Journal Article

Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome

Chahrazed El Hamel, Antoine Thierry, Patrick Trouillas, Frank Bridoux, Claire Carrion, Nathalie Quellard, Jean-Michel Goujon, Jean-Claude Aldigier, Jean-Marc Gombert, Michel Cogné and Guy Touchard

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 25, issue 9, pages 2982-2990
Published in print September 2010 | ISSN: 0931-0509
Published online March 2010 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfq129
Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome

Show Summary Details

Preview

Background. Crystal-storing histiocytosis (CSH) is a poorly described complication of monoclonal gammopathy featuring histiocyte lysosomal storage of κ light chain (κLC) crystals. Although CSH is usually associated with systemic manifestations, renal involvement is uncommon.

Methods. To investigate the molecular mechanisms implicated in κLC crystallization, we performed immunopathological and molecular studies in three patients with CSH and renal Fanconi syndrome (CSH/FS). The Vκ sequences were determined, and resulting molecular models were compared with previously reported myeloma-associated FS κLC sequences.

Results. All patients presented with chronic tubulo-interstitial nephritis and renal FS with accumulation of monoclonal κLC 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 Vκ 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.

Conclusion. Although CSH/FS and myeloma-associated FS are closely related disorders, peculiar mutations in the V domains of CSH/FS monoclonal κLCs, different from those in myeloma-associated FS, may account for crystal morphology, predominant accumulation within histiocytes and multiple organ involvement in CSH.

Keywords: crystal-storing histiocytosis; Fanconi syndrome; molecular modelling; monoclonal κ light chains

Journal Article.  5336 words.  Illustrated.

Subjects: Nephrology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.