C3 glomerulopathy (C3GP) including dense deposit disease (DDD) is mediated by abnormal activation of the alternative complement pathway (ACP). In children and young adults, mutations of complement or complement regulatory proteins are the major causative factors but in adults there appears to be an increased incidence of monoclonal gammopathy and it has been proposed that the paraprotein is functioning as a C3 nephritic factor or through other unknown mechanisms resulting in abnormal ACP activity.
The presence of significant immunoglobulin staining is associated with an immune complex etiology whereas dominant staining for C3 with little or no immunoglobulin is more indicative of abnormal activation of the alternative complement pathway (ACP).
Monoclonal gammopathy has been associated with both immune complex type MPGN and C3GP, including DDD. The incidence of monoclonal gammopathy in patients with MPGN may be as high as 41% .