Tetramer Bence Jones Protein in the Immunoproliferative Diseases: Angioimmunoblastic Lymphadenopathy, Primary Amyloidosis, and Multiple Myeloma

Kosaka, Masaaki; Y, Iishi; Okagawa, Kazuto; Saito, Shiro; Sugihara, Junichi; Muto, Yasutoshi

doi:10.1093/ajcp/91.6.639

Cited by 11 publications

(3 citation statements)

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“…4 and subsequent MS/MS analysis of the peptides confirmed that the protein present in each peak was derived from the same lambda light chain constant region (peaks A-C each contained YAASSYLSLTPEQWK and AAPSVTLFPPSSEEL-QANK derived from the Ig λ Chain C Regions). The presence of covalent dimers and dimers of covalent dimers in lambda Bence Jones proteins has been confirmed by others utilizing electrophoretic, gel filtration, and ultracentrifugal analyses (Kosaka et al, 1989). This is the first example, however, of Bence Jones protein analysis utilizing mass spectral analysis under nondenaturing conditions.…”

Section: Discussionmentioning

confidence: 56%

Characterization of amyloidogenic immunoglobulin light chains directly from serum by on‐line immunoafﬁnity isolation

Bergen¹,

Abraham²,

Johnson³

et al. 2004

Biomedical Chromatography

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Primary systemic amyloidosis (AL) is characterized by the overproduction of immunoglobulin light chain proteins by a monoclonal, terminally differentiated B-lymphocyte or plasma cell clone. The free immunoglobulin light chains are deposited in an abnormal conformation as amyloid in a variety of organs in the body. The mechanism of amyloid formation is not well understood, but appears to be associated with some form of cleavage of the immunoglobulin light chain with subsequent aggregate formation. In an attempt to characterize the structure of amyloid-forming light chain proteins we developed an on-line immunoaffinity purification and subsequent characterization of free kappa and free lambda immunoglobulin light chains by electrospray ionization mass spectrometry. The methodology is totally automated and requires 20 micro L of serum. Mass spectral analysis of Bence Jones proteins under non-denaturing conditions was also utilized to examine the tertiary and quaternary structure of light chain proteins and clearly shows covalent dimer formation of lambda type light chain. This type of on-line assay may prove helpful in elucidating distinguishing features capable of discriminating AL from benign monoclonal gammopathies of undetermined significance as well as diagnosing AL.

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Section: Discussionmentioning

confidence: 56%

Characterization of amyloidogenic immunoglobulin light chains directly from serum by on‐line immunoafﬁnity isolation

Bergen¹,

Abraham²,

Johnson³

et al. 2004

Biomedical Chromatography

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“…Notably the level of BJ protein was relatively high also for the other BJ sets, for example, BJ1 1 and BJ2 (Table ), but thermal transition at 57 °C was not observed. Therefore, we hypothesize that this transition in BJ4 thermograms is due to free BJ protein, while in the other sets the endotherm of its bound state (ligated to other proteins such as Tamm Horsfall glycoprotein or forming BJ aggregates (dimers and tetramers)) might be shifted to higher temperatures and cannot be resolved in the thermogram of the complex serum fluid.…”

Section: Resultsmentioning

confidence: 99%

Calorimetric Markers of Bence Jones and Nonsecretory Multiple Myeloma Serum Proteome

et al. 2014

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The present work provides a thermodynamic description of blood serum from patients diagnosed with Bence Jones myeloma (BJMM) and nonsecretory myeloma (NSMM) by means of differential scanning calorimetry (DSC), serum protein electrophoresis, and free light chain assay. Specific alterations in the thermodynamic behavior of both BJMM and NSMM proteome have been revealed. On the basis of the transition temperature of the main transition in the calorimetric profiles and the shape similarity criterion, we defined BJMM and NSMM sets/subsets of thermograms with very similar thermodynamic features. We show that some of the BJMM and NSMM subsets correlate with previously defined secretory myeloma subsets (Todinova et al. Anal. Chem. 2011, 83, 7992). The established analogies strongly suggest that common molecular markers contribute to the calorimetric profiles of the different, secretory and nonsecretory, myeloma types; our data show robust evidence that these are ligands stabilizing the major serum proteins. We demonstrate that the DSC approach might be highly beneficial, especially for NSMM patients, since the characteristic modifications in the DSC profiles might serve as calorimetric markers when no monoclonal proteins can be detected in the bloodstream and the diagnosis heavily relies on invasive methods.

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“…We posit that the tissue deposition of light chains is governed by the concepts of mass action that underlie all molecular interactions. In addition, host-related factors, such as dehydration, affect cast formation in the kidney (20)(21)(22). Since this process results in an increased protein concentration-a condition we find to increase aggregate formation exponentially-this phenomenon could account for the renal tubular deposition of an apparently nontoxic Bence Jones protein (23).…”

Section: Methodsmentioning

confidence: 89%

Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition.

Myatt

Westholm

Weiss

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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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 dis -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 oflow concentrations ofurea. 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 hh 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 dlagnostic 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 aggregtion and the treatment of those invariably fatal disorders associated with pathologic lightchain deposition.The human light-chain-related renal and systemic diseasesmyeloma (cast) nephropathy, light-chain deposition disease, and immunocyte-derived (primary or AL) amyloidosisresult from the pathologic deposition of monoclonal light chains (i.e., Bence Jones proteins) in the form of casts, basement membrane precipitates, or fibrils, respectively (1). These light-chain deposits ultimately result in the impairment ofrenal and other organ function and account for much ofthe morbidity and mortality found in patients with these disorders. The fact that pathologic light-chain deposits are not an invariant accompaniment of clinical or experimental (1) Bence Jones proteinuria and are not necessarily directly related to the amount of monoclonal light chain synthesized or excreted implies that certain light chains are inherently nephrotoxic or amyloidogenic.Several in vitro and in vivo models have been devised that provide an experimental means to assess the pathologic potential of Bence Jones proteins (2-5). For example, in one model we demonstrated that the injection into mice ofcertain Bence Jones proteins resulted in the deposition in the mouse kidney of the human proteins in the form of tubular casts, basement membrane precipitates, crystals, or amyloid fibrils (6). Through studies involving >40 different Bence Jones proteins, we found that the renal lesions induced experimentally were comparable to those of patients from whom the proteins were derived and that the experimental mouse model was capable of differentiating "nephrotoxic" from "...

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Tetramer Bence Jones Protein in the Immunoproliferative Diseases: Angioimmunoblastic Lymphadenopathy, Primary Amyloidosis, and Multiple Myeloma

Cited by 11 publications

References 0 publications

Characterization of amyloidogenic immunoglobulin light chains directly from serum by on‐line immunoafﬁnity isolation

Characterization of amyloidogenic immunoglobulin light chains directly from serum by on‐line immunoafﬁnity isolation

Calorimetric Markers of Bence Jones and Nonsecretory Multiple Myeloma Serum Proteome

Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition.

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