TY - JOUR
T1 - Dense deposit disease associated with monoclonal gammopathy of undetermined significance
AU - Sethi, Sanjeev
AU - Sukov, William R.
AU - Zhang, Yuzhou
AU - Fervenza, Fernando C.
AU - Lager, Donna J.
AU - Miller, Dylan V.
AU - Cornell, Lynn D.
AU - Krishnan, Srivilliputtur G.Santhana
AU - Smith, Richard J.H.
N1 - Funding Information:
Support: This research was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases grant DK074409 to Drs Sethi and Smith.
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Dense deposit disease
KW - Index Words
KW - factor H antibodies
KW - monoclonal gammopathy
KW - monoclonal gammopathy of undetermined significance (MGUS)
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U2 - 10.1053/j.ajkd.2010.06.021
DO - 10.1053/j.ajkd.2010.06.021
M3 - Article
C2 - 20832153
AN - SCOPUS:77958488596
SN - 0272-6386
VL - 56
SP - 977
EP - 982
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 5
ER -