Light, light and heavy, and heavy chain deposition diseases (LCDD, LHCDD and
HCDD, respectively) belong to a family of diseases featuring deposition in the kidney of a monoclonal
immunoglobulin (Ig) or its isolated subunits, which also includes light chain
amyloidosis, non-
amyloid fibrillary and immunotactoid
glomerulonephritis, and cryoglobulinemic
glomerulonephritis. In clinical and pathologic terms, LCDD, LHCDD and
HCDD display essentially similar characteristics, such as involvement of multiple organs, prominent renal involvement with severe
renal failure, diabetes-like
nodular glomerulosclerosis, marked thickening of tubular basement membranes, and monotypic deposits of
Ig light chains (mostly κ) and/or heavy chains (mostly γ) that feature a non-organized granular, electron-dense appearance by electron microscopy. The most common cause is myeloma, although in a fair proportion of cases there is no (clinically) patent
hematological disease. Recent progress has been made in understanding the molecular mechanisms of Ig-chain deposition and extracellular matrix accumulation, which opens up new therapeutic avenues in addition to eradication of the Ig-secreting plasma cell clone. Because these diseases represent a model of glomerular and interstitial
fibrosis that is induced by a single molecule species, a better understanding of their pathophysiological mechanism may help unraveling the pathomechanisms of kidney
fibrosis and renal
disease progression.