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Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition.
Proc Natl Acad Sci U S A. 1994 Apr 12; 91(8):3034-8.PN

Abstract

The deposition of certain Bence Jones proteins as tubular casts, basement membrane precipitates, or amyloid fibrils results in the human light-chain-associated renal and systemic diseases--myeloma (cast) nephropathy, light-chain deposition disease, and immunocyte-derived (primary or AL) amyloidosis. To determine if light-chain nephrotoxicity or amyloidogenicity is related to the propensity of these components to form high molecular weight aggregates under physiological conditions, we used a size-exclusion chromatographic system to study 40 different Bence Jones proteins. Each samples was tested over a wide range of protein concentration in three different buffers varying in pH, osmolality, and the presence or absence of low concentrations of urea. Thirty-three of the 35 proteins found clinically and/or experimentally to form in vivo pathologic light-chain deposits were shown to undergo high-order self-association and form high molecular weight aggregates. In contrast, of five nonpathologic proteins, one showed polymerization under the chromatographic conditions used. The correlation between the in vivo results achieved by size-exclusion chromatography and that found in vivo provides (i) a rapid diagnostic method to identify potential nephrotoxic or amyloidogenic Bence Jones proteins and (ii) an experimental means to gain new insight into the physicochemical basis of light-chain aggregation and the treatment of those invariably fatal disorders associated with pathologic light-chain deposition.

Authors+Show Affiliations

Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, IL 60439-4833.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

8159701

Citation

Myatt, E A., et al. "Pathogenic Potential of Human Monoclonal Immunoglobulin Light Chains: Relationship of in Vitro Aggregation to in Vivo Organ Deposition." Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 8, 1994, pp. 3034-8.
Myatt EA, Westholm FA, Weiss DT, et al. Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition. Proc Natl Acad Sci U S A. 1994;91(8):3034-8.
Myatt, E. A., Westholm, F. A., Weiss, D. T., Solomon, A., Schiffer, M., & Stevens, F. J. (1994). Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition. Proceedings of the National Academy of Sciences of the United States of America, 91(8), 3034-8.
Myatt EA, et al. Pathogenic Potential of Human Monoclonal Immunoglobulin Light Chains: Relationship of in Vitro Aggregation to in Vivo Organ Deposition. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3034-8. PubMed PMID: 8159701.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition. AU - Myatt,E A, AU - Westholm,F A, AU - Weiss,D T, AU - Solomon,A, AU - Schiffer,M, AU - Stevens,F J, PY - 1994/4/12/pubmed PY - 1994/4/12/medline PY - 1994/4/12/entrez SP - 3034 EP - 8 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 91 IS - 8 N2 - The deposition of certain Bence Jones proteins as tubular casts, basement membrane precipitates, or amyloid fibrils results in the human light-chain-associated renal and systemic diseases--myeloma (cast) nephropathy, light-chain deposition disease, and immunocyte-derived (primary or AL) amyloidosis. To determine if light-chain nephrotoxicity or amyloidogenicity is related to the propensity of these components to form high molecular weight aggregates under physiological conditions, we used a size-exclusion chromatographic system to study 40 different Bence Jones proteins. Each samples was tested over a wide range of protein concentration in three different buffers varying in pH, osmolality, and the presence or absence of low concentrations of urea. Thirty-three of the 35 proteins found clinically and/or experimentally to form in vivo pathologic light-chain deposits were shown to undergo high-order self-association and form high molecular weight aggregates. In contrast, of five nonpathologic proteins, one showed polymerization under the chromatographic conditions used. The correlation between the in vivo results achieved by size-exclusion chromatography and that found in vivo provides (i) a rapid diagnostic method to identify potential nephrotoxic or amyloidogenic Bence Jones proteins and (ii) an experimental means to gain new insight into the physicochemical basis of light-chain aggregation and the treatment of those invariably fatal disorders associated with pathologic light-chain deposition. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/8159701/Pathogenic_potential_of_human_monoclonal_immunoglobulin_light_chains:_relationship_of_in_vitro_aggregation_to_in_vivo_organ_deposition_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=8159701 DB - PRIME DP - Unbound Medicine ER -