Dense deposit disease associated with monoclonal gammopathy of undetermined significance.
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.
Sethi
Sanjeev
S
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. sethi.sanjeev@mayo.edu
Sukov
William R
WR
Zhang
Yuzhou
Y
Fervenza
Fernando C
FC
Lager
Donna J
DJ
Miller
Dylan V
DV
Cornell
Lynn D
LD
Krishnan
Srivilliputtur G Santhana
SG
Smith
Richard J H
RJ
D001323:Autoantibodies / Q000276:immunology*; D001706:Biopsy; D017242:Complement Factor H / Q000276:immunology* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007678:Kidney Glomerulus / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010265:Paraproteinemias / Q000150:complications* / Q000175:diagnosis / Q000276:immunology
D001323:Autoantibodies; D017242:Complement Factor H