title: Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome.
abstract: BACKGROUND
  Crystal-storing histiocytosis (CSH) is a poorly described complication of monoclonal gammopathy featuring histiocyte lysosomal storage of kappa light chain (kappa LC) crystals. Although CSH is usually associated with systemic manifestations, renal involvement is uncommon.
  
  
  METHODS
  To investigate the molecular mechanisms implicated in kappa LC crystallization, we performed immunopathological and molecular studies in three patients with CSH and renal Fanconi syndrome (CSH/FS). The V kappa sequences were determined, and resulting molecular models were compared with previously reported myeloma-associated FS kappa LC sequences.
  
  
  RESULTS
  All patients presented with chronic tubulo-interstitial nephritis and renal FS with accumulation of monoclonal kappa LC crystals within proximal tubular cells. They showed peri-renal and interstitial infiltration by histiocytes containing eosinophilic crystalline inclusions (pseudo-pseudo-Gaucher cells). LC sequences were determined and assigned to their germline counterparts, in strong homology with previously reported myeloma-associated FS sequences. Comparison of CSH/FS V kappa domain 3D structures with the germline-encoded structures and those from patients with myeloma-associated FS underlined distinct hydrophobic residues exposed to the solvent in two patients, likely favouring the formation of a variant form of crystals that may further resist degradation after phagocytosis.
  
  
  CONCLUSIONS
  Although CSH/FS and myeloma-associated FS are closely related disorders, peculiar mutations in the V domains of CSH/FS monoclonal kappa LCs, different from those in myeloma-associated FS, may account for crystal morphology, predominant accumulation within histiocytes and multiple organ involvement in CSH.
authors.affiliation: Université de Limoges, Centre National de la Recherche Scientifique (CNRS) UMR 6101, CHU Limoges, France.
authors.forename: Chahrazed
authors.initials: C
authors.lastname: El Hamel
authors.forename: Antoine
authors.initials: A
authors.lastname: Thierry
authors.forename: Patrick
authors.initials: P
authors.lastname: Trouillas
authors.forename: Frank
authors.initials: F
authors.lastname: Bridoux
authors.forename: Claire
authors.initials: C
authors.lastname: Carrion
authors.forename: Nathalie
authors.initials: N
authors.lastname: Quellard
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Goujon
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Aldigier
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gombert
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
authors.forename: Guy
authors.initials: G
authors.lastname: Touchard
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D003460:Crystallization; D005198:Fanconi Syndrome / Q000145:classification / Q000209:etiology / Q000473:pathology*; D005260:Female; D015614:Histiocytosis / Q000150:complications / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry* / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry* / Q000235:genetics; D007674:Kidney Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000150:complications / Q000235:genetics / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D017386:Sequence Homology, Amino Acid
chemical_list: D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains