Specific impairment of proximal tubular cell proliferation by a monoclonal κ light chain responsible for Fanconi syndrome. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nephrology Dialysis Transplantation Année : 2012

Specific impairment of proximal tubular cell proliferation by a monoclonal κ light chain responsible for Fanconi syndrome.

Résumé

Background Fanconi syndrome (FS) is a rare renal disorder featuring proximal tubule dysfunction that may occur following tubular reabsorption of a monoclonal light chain (LC), in patients with multiple myeloma. FS may precede the recognition of multiple myeloma by several years. In most cases, crystalline inclusions of monoclonal κ LCs are observed within the lysosomes of proximal tubular cells (PTCs) and probably participate in their functional alteration. Methods To investigate the mechanism implicated in proximal tubule dysfunction, we compared the effects of κ LC-CHEB obtained from a patient with myeloma-associated FS to those of control κ LC-BON obtained from a patient without evidence of FS, on the viability and proliferation of two different PTC lines. Results Our data suggest that the tubular atrophy in myeloma-associated FS does not result from increased apoptosis of PTCs, but from their impaired capacity to proliferate and renew. Indeed, in vitro incubation of cultured PTCs with physiological amounts of the nephrotoxic κ LC-CHEB was sufficient to cause a depression in DNA synthesis and in cell proliferation. This effect was observed neither with control κ LC-BON nor in the absence of κ LC. Conclusions The reduced turnover of PTCs may affect tubular repair and regeneration. In addition, the reduced proliferation of myeloma cells producing the same monoclonal κ LC might explain the frequent association of FS with smoldering multiple myeloma.

Domaines

Immunologie
Fichier non déposé

Dates et versions

hal-00779410 , version 1 (22-01-2013)

Identifiants

Citer

Chahrazed El Hamel, Jean-Claude Aldigier, Christelle Oblet, Brice Laffleur, Franck Bridoux, et al.. Specific impairment of proximal tubular cell proliferation by a monoclonal κ light chain responsible for Fanconi syndrome.. Nephrology Dialysis Transplantation, 2012, 27 (12), pp.4368-77. ⟨10.1093/ndt/gfs261⟩. ⟨hal-00779410⟩
41 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More