Monoclonal immunoglobulin light and heavy chain deposition diseases: molecular models of common renal diseases.
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.
Pierre
P
Ronco
Emmanuelle
E
Plaisier
Pierre
P
Aucouturier
D005109:Extracellular Matrix / Q000276:immunology / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D007674:Kidney Diseases / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008958:Models, Molecular
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains