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 Printable version |
Plasma cell dyscrasia-related renal diseases |
Hématologie. Volume 8, Number 2, 129-40, Mars - Avril 2002, Revues et mini-revues
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 Résumé
Article gratuit
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Author(s) : Pascal Meier, Béatrice Mougenot, Pierre Aucouturier , Pierre Ronco |
Summary : The spectrum of renal diseases with deposition or precipitation of monoclonal Ig related material is wide, and such a diversity is probably due to unusual physicochemical properties of the secreted Ig. These properties account for recurrence of the initial renal disease after transplantation and for correlations between the type of renal lesions induced in mice injected with human nephritogenic light chains and the initial nephropathy. Since the first description of myeloma casts, considerable progress has been made in the understanding of the pathophysiology of Ig related renal diseases. In myeloma cast nephropathy, filtered light chains bind to a peptidic segment of nine aminoacids of the Tamm-Horsfall glycoprotein (THP) (probably through a sequence in their CDR3 loop), and their interaction triggers cast formation in the distal nephron where THP is produced. The proximal tubular lesions seen in kappa chain Fanconi's syndrome (FS) are characterized by crystal formation. Fanconi's syndrome light chains are remarkable for restricted usage of two VkappaI genes with unusual amino-acid substitutions, and for resistance of the variable domain Vkappa to proteolysis. Not all light chains are amyloidogenic but the following characteristics are predisposing factors: lambda isotype, VlambdaVI variability subgroup, unusual substitution by acid aminoacids in the variable region Vlambda, and tendency to dimerize. At variance with amyloidosis, lesions in monoclonal Ig deposition disease are characterized by a dramatic accumulation of extracellular matrix. Light chain deposition disease is characterized by predominance of kappa chains, abnormal glycosylation that occurs in about 20% of patients and is correlated with very low circulating light chain levels, and presence in CDR1 loop of hydrophobic residues that might increase the light chain propensity to precipitate in tissues. In the recently described heavy chain deposition disease, the nephritogenic heavy chain is remarkable for the deletion of the CH1 domain. However, CH1 deletion seems necessary but not sufficient for deposition, and it is likely that the VH also contributes to tissue deposition. Some of the above physicochemical properties open new therapeutic avenues for the treatment of plasma cell dyscrasia-related renal diseases. |
Keywords : plasma cell dyscrasia, cast nephropathy, Fanconi's syndrome, monoclonal immunoglobulin deposition disease, light chain deposition disease, heavy chain deposition disease, AL amyloidosis, immunotactoid glomerulopathy. |
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