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Light chain cardiomyopathy. Structural analysis of the light chain tissue deposits.
Am J Pathol. 1996 May; 148(5):1397-406.AJ

Abstract

Cardiomyopathy due to monoclonal light chain deposits is a complication of plasma cell disorders. The deposits may be either fibrillar as in light chain amyloid or nonfibrillar as in light chain deposition disease. The reasons for these structural differences are still unknown. We characterized the myocardial deposits by immunohistochemical examination of sections and extraction and biochemical analysis of the tissue deposits in a patient (MCM) who died of myeloma and systemic light chain deposition disease. Amino acid sequence analysis of the extracted nonfibrillar MCM kappa-light chain reveals that it belongs to the L12a germline subset of the kappa(I) protein and contains five distinctive amino acid substitutions (three in the framework region III and two in the complementarity-determining region III) that have not been reported previously in the same positions in other kappa(I) light chains. The theoretically determined isoelectric point (pI 8.21) of the MCM light chain is high compared with the low isoelectric point of other Bence Jones proteins from subjects without light chain deposition disease. The diffuse binding to basement membranes and the high isoelectric point of the MCM kappa-light chain suggest electrostatic interaction as a possible mechanism of tissue deposition. The spatial locations of the five distinctive residues and a sixth rare substitution of the MCM protein modeled on the backbone structure of REI, a kappa(I)-soluble Bence Jones light chain of known three-dimensional structure, may be responsible for protein destabilization, partial unfolding, and aggregation leading to tissue deposition.

Authors+Show Affiliations

Department of Pathology, New York University Medical Center, New York 10016, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8623912

Citation

Gallo, G, et al. "Light Chain Cardiomyopathy. Structural Analysis of the Light Chain Tissue Deposits." The American Journal of Pathology, vol. 148, no. 5, 1996, pp. 1397-406.
Gallo G, Goñi F, Boctor F, et al. Light chain cardiomyopathy. Structural analysis of the light chain tissue deposits. Am J Pathol. 1996;148(5):1397-406.
Gallo, G., Goñi, F., Boctor, F., Vidal, R., Kumar, A., Stevens, F. J., Frangione, B., & Ghiso, J. (1996). Light chain cardiomyopathy. Structural analysis of the light chain tissue deposits. The American Journal of Pathology, 148(5), 1397-406.
Gallo G, et al. Light Chain Cardiomyopathy. Structural Analysis of the Light Chain Tissue Deposits. Am J Pathol. 1996;148(5):1397-406. PubMed PMID: 8623912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Light chain cardiomyopathy. Structural analysis of the light chain tissue deposits. AU - Gallo,G, AU - Goñi,F, AU - Boctor,F, AU - Vidal,R, AU - Kumar,A, AU - Stevens,F J, AU - Frangione,B, AU - Ghiso,J, PY - 1996/5/1/pubmed PY - 1996/5/1/medline PY - 1996/5/1/entrez SP - 1397 EP - 406 JF - The American journal of pathology JO - Am J Pathol VL - 148 IS - 5 N2 - Cardiomyopathy due to monoclonal light chain deposits is a complication of plasma cell disorders. The deposits may be either fibrillar as in light chain amyloid or nonfibrillar as in light chain deposition disease. The reasons for these structural differences are still unknown. We characterized the myocardial deposits by immunohistochemical examination of sections and extraction and biochemical analysis of the tissue deposits in a patient (MCM) who died of myeloma and systemic light chain deposition disease. Amino acid sequence analysis of the extracted nonfibrillar MCM kappa-light chain reveals that it belongs to the L12a germline subset of the kappa(I) protein and contains five distinctive amino acid substitutions (three in the framework region III and two in the complementarity-determining region III) that have not been reported previously in the same positions in other kappa(I) light chains. The theoretically determined isoelectric point (pI 8.21) of the MCM light chain is high compared with the low isoelectric point of other Bence Jones proteins from subjects without light chain deposition disease. The diffuse binding to basement membranes and the high isoelectric point of the MCM kappa-light chain suggest electrostatic interaction as a possible mechanism of tissue deposition. The spatial locations of the five distinctive residues and a sixth rare substitution of the MCM protein modeled on the backbone structure of REI, a kappa(I)-soluble Bence Jones light chain of known three-dimensional structure, may be responsible for protein destabilization, partial unfolding, and aggregation leading to tissue deposition. SN - 0002-9440 UR - https://www.unboundmedicine.com/medline/citation/8623912/Light_chain_cardiomyopathy__Structural_analysis_of_the_light_chain_tissue_deposits_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/8623912/ DB - PRIME DP - Unbound Medicine ER -