Pathogenic potential of human monoclonal immunoglobulin light chains

Relationship of in vitro aggregation to in vivo organ deposition

Elizabeth A. Myatt, Florence A. Westholm, Deborah T. Weiss, Alan Solomon, Marianne Schiffer, Fred J. Stevens

Research output: Contribution to journalArticle

58 Citations (Scopus)

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 sample 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 vitro 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.

Original languageEnglish (US)
Pages (from-to)3034-3038
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number8
DOIs
StatePublished - Apr 12 1994

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Immunoglobulin Light Chains
Bence Jones Protein
Light
Molecular Weight
Amyloidogenic Proteins
Proteins
Amyloidosis
Amyloid
Basement Membrane
Polymerization
Osmolar Concentration
Gel Chromatography
Urea
In Vitro Techniques
Buffers
Kidney

All Science Journal Classification (ASJC) codes

  • General

Cite this

Pathogenic potential of human monoclonal immunoglobulin light chains : Relationship of in vitro aggregation to in vivo organ deposition. / Myatt, Elizabeth A.; Westholm, Florence A.; Weiss, Deborah T.; Solomon, Alan; Schiffer, Marianne; Stevens, Fred J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 8, 12.04.1994, p. 3034-3038.

Research output: Contribution to journalArticle

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