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Generalized crystal-storing histiocytosis associated with monoclonal gammopathy: molecular analysis of a disorder with rapid clinical course and review of the literature

Item Type:Article
Title:Generalized crystal-storing histiocytosis associated with monoclonal gammopathy: molecular analysis of a disorder with rapid clinical course and review of the literature
Creators Name:Lebeau, A. and Zeindl-Eberhart, E. and Mueller, E.C. and Mueller-Hoecker, J. and Jungblut, P.R. and Emmerich, B. and Loehrs, U.
Abstract:Crystal-storing histiocytosis (CSH) is a rare event in disorders associated with monoclonal gammopathy. The intracellular crystal formation is almost always accompanied by the expression of κ light chains. However, the exact mechanism for the storage has not been clarified until now. We report a case of generalized CSH in a 73-year-old man who presented with IgA κ paraproteinemia and paraproteinuria. The initially observed CSH in the bone marrow biopsy was associated with the clinical and pathomorphologic features of a monoclonal gammopathy of undetermined significance. The progression of disease could not be affected by steroid therapy and the patient died of septic shock 7 months after detection of CSH. At the time of autopsy there was evidence for multiple myeloma and generalized CSH. Two-dimensional gel electrophoresis of liver tissue combined with immunoblotting revealed the massive storage of heavy chains of {alpha} type and light chains of {kappa} type, each in a monoclonal pattern. Analysis of the stored {kappa} light chain by nanoelectrospray-ionization mass spectrometry indicated that it belongs to the variable KI variability subgroup. We identified some unusual amino acid substitutions including Leu59, usually Important for hydrophobic interactions within a protein, at a position where it has never been previously described in plasma cell disorders. In conclusion, we present the first case of CSH with molecular identification of the stored {kappa} subgroup and detection of unusual amino acid substitutions. Our results suggest that conformational alterations induced by amino acid exchanges represent a crucial pathogenic factor in CSH.
Keywords:Biopsy, Bone Marrow, Fatal Outcome, Immunoglobulin Genes, Immunoglobulin A, Immunoglobulin {kappa}-Chains, Langerhans-Cell Histiocytosis, Multiple Myeloma, Paraproteinemias
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:100
Number:5
Page Range:1817-1827
Date:1 September 2002
Official Publication:http://bloodjournal.hematologylibrary.org/cgi/content/abstract/100/5/1817
PubMed:View item in PubMed

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