Immunoglobulin light (heavy)-chain deposition disease: from molecular medicine to pathophysiology-driven therapy.
Light-, light- and heavy-, and heavy-chain deposition diseases belong to a family of diseases that include light-chain (AL)-amyloid, nonamyloid fibrillary and immunotactoid glomerulonephritis, and cryoglobulinemic glomerulonephritis, in which monoclonal Ig or their subunits become deposited in kidney. In clinical and pathologic terms, light-, light- and heavy-, and heavy-chain deposition diseases essentially are similar and are characterized by prominent renal involvement with severe renal failure; extrarenal manifestations; diabetes-like nodular glomerulosclerosis; marked thickening of tubular basement membranes; and monotypic deposits of light chain, mostly kappa, and/or heavy chain that feature a nonorganized granular, electron-dense appearance by electron microscopy. The most common cause is myeloma. Recent progress has been made in the understanding of the molecular pathomechanisms 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 pathomechanisms may help to unravel the pathophysiology of kidney fibrosis and renal disease progression.
Ronco
Pierre
P
INSERM UMR S 702, Université Pierre et Marie Curie-Paris 6, Paris, France. pierre.ronco@tnn.aphp.fr
Plaisier
Emmanuelle
E
Mougenot
Béatrice
B
Aucouturier
Pierre
P
D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D010265:Paraproteinemias / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D033581:Stem Cell Transplantation
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains