title: Specific impairment of proximal tubular cell proliferation by a monoclonal κ light chain responsible for Fanconi syndrome.
abstract: 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.
authors.affiliation: Université de Limoges, Laboratoire Contrôle de la réponse immune B et lymphoproliférations, Centre National de la Recherche Scientifique (CNRS), Unité mixte de Recherche (UMR) 7276, CHU Limoges, France. chahrazed.elhamel@unilim.fr
authors.forename: Chahrazed
authors.initials: C
authors.lastname: El Hamel
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Aldigier
authors.forename: Christelle
authors.initials: C
authors.lastname: Oblet
authors.forename: Brice
authors.initials: B
authors.lastname: Laffleur
authors.forename: Frank
authors.initials: F
authors.lastname: Bridoux
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
mesh_terms: D001284:Atrophy; D049109:Cell Proliferation; D002478:Cells, Cultured; D005198:Fanconi Syndrome / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000473:pathology*
chemical_list: D007145:Immunoglobulin kappa-Chains