PATHOGENIC POTENTIAL OF HUMAN MONOCLONAL IMMUNOGLOBULIN LIGHT-CHAINS - RELATIONSHIP OF IN-VITRO AGGREGATION TO IN-VIVO ORGAN DEPOSITION

Citation
Ea. Myatt 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 Statesof America, 91(8), 1994, pp. 3034-3038
Citations number
33
Categorie Soggetti
Multidisciplinary Sciences
ISSN journal
00278424
Volume
91
Issue
8
Year of publication
1994
Pages
3034 - 3038
Database
ISI
SICI code
0027-8424(1994)91:8<3034:PPOHMI>2.0.ZU;2-Y
Abstract
The deposition of certain Bence Jones proteins as tubular casts, basem ent membrane precipitates, or amyloid fibrils results in the human fig ht-chain-associated renal and systemic diseases-myeloma (cast) nephrop athy, light-chain deposition disease, and immunocyte-derived (primary Gr AL) amyloidosis. To determine if light-chain nephrotoxicity or amyl oidogenicity is related to the propensity of these components to form high molecular weight aggregates under physiological conditions, we us ed a size-exclusion chromatographic system to study 40 different Bence Jones proteins. Each sample was tested over a wide range of protein c oncentration in three different buffers varying in pH, osmolality, and the presence or absence of low concentrations of urea. Thirty-three o f the 35 proteins found clinically and/or experimentally to form in vi vo pathologic light-chain deposits were shown to undergo high-order se lf-association and form high molecular weight aggregates. In contrast, of five nonpathologic proteins, one showed polymerization under the c hromatographic conditions used. The correlation between the in vitro r esults achieved by size-exclusion chromatography and that found in viv o provides (i) a rapid diagnostic method to identify potential nephrot oxic or amyloidogenic Bence Jones proteins and (ii) an experimental me ans to gain new insight into the physicochemical basis of light-chain aggregation and the treatment of those invariably fatal disorders asso ciated with pathologic light-chain deposition.