help button home button Am J Pathol International Conference on Pathology of Chest Diseases
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vidal, R.
Right arrow Articles by Gallo, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vidal, R.
Right arrow Articles by Gallo, G.
(American Journal of Pathology. 1999;155:2009-2017.)
© 1999 American Society for Investigative Pathology

Regular Articles

Somatic Mutations of the L12a Gene in V-{kappa}1 Light Chain Deposition Disease

Potential Effects on Aberrant Protein Conformation andDeposition

Ruben Vidal*, Fernando Goñi*,{dagger}, Fred Stevens{ddagger}, Pierre Aucouturier*, Asok Kumar*, Blas Frangione*, Jorge Ghiso* and Gloria Gallo*

From the Department of Pathology,*
New York University School of Medicine, New York, New York; the Facultad de Química,{dagger}
Universidad de la República Oriental del Uruguay, Montevideo, Uruguay; and the Biosciences Division,{ddagger}
Argonne National Laboratory, Argonne, Illinois

Light chain deposition disease (LCDD) and light chain amyloidosis (AL) are disorders of monoclonal immunoglobulin deposition in which normally soluble serum precursors form insoluble deposits in tissues. A common feature in both is the clonal proliferation of B-cells that produce pathogenic light chains. However, the deposits in LCDD differ from those in AL in that they are ultrastructurally granular rather than fibrillar and do not bind Congo red or colocalize with amyloid P component or apolipoprotein E. The reason(s) for their differences are unknown but are likely multifactorial and related to their protein conformation and their interaction with other molecules and tissue factors in the microenvironment. Knowledge of the primary structure of the light chains in LCDD is very limited. In the present study two new {kappa}1 light chains from patients with LCDD are described and compared to seven other reported {kappa}-LCDD proteins. The N-terminal amino acid sequences of light chain GLA extracted from the renal biopsy and light chain CHO from myocardial tissue were each identical to the respective light chains isolated from the urines and to the V-region amino acid sequences translated from the cloned cDNAs obtained from bone marrow cells. The germline V-region sequences, determined from the genomic DNA in both and in MCM, a previously reported {kappa}1 LCDD light chain, were identical and related to the L12a germline gene. The expressed light chains in all three exhibit amino acid substitutions that arise from somatic mutation and result in increased hydrophobicity with the potential for protein destabilization and disordered conformation.




This article has been cited by other articles:


Home page
 CJASNHome page
D. J. Salant, V. Sanchorawala, and V. D. D'Agati
A Case of Atypical Light Chain Deposition Disease--Diagnosis and Treatment
Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(4): 858 - 867.
[Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
H. T. Blumenthal
Amyloidosis: A Universal Disease of Aging?
J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2004; 59(4): M361 - M369.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by the American Society for Investigative Pathology.