Constant Region of a κ III Immunoglobulin Light Chain as a Major AL‐Amyloid Protein

Engvig, J P; Olsen, Karen Ege; Gislefoss, Randi Elin; Sletten, Knut; Wahlström, Ola; Westermark, Per

doi:10.1046/j.1365-3083.1998.00352.x

Cited by 45 publications

(34 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, it is commonly accepted that the fragments of variable domains of monoclonal Ig light chains play a major role in fibril formation. In this respect, our findings support some recent studies suggesting that the presence of constant region fragments in amyloid deposits may be more common than formerly held and their role in fibril formation was underestimated [6,16,24,31,34].…”

Section: Discussionsupporting

confidence: 91%

Co-deposition of amyloidogenic immunoglobulin light and heavy chains in localized pulmonary amyloidosis

et al. 2005

View full text Add to dashboard Cite

Localized pulmonary amyloidosis is a rare condition whose pathogenesis is insufficiently understood. In the present study, we report a case of localized pulmonary amyloidosis associated with lung-restricted lymphoplasmacytoid lymphoma, monoclonal for immunoglobulin (Ig) G lambda (lambda). Biochemical microtechniques have been applied for extraction, purification, and characterization of amyloid proteins. Surprisingly, chemical analysis of these proteins revealed a not-previously-described case of combined deposits containing Ig fragments of gamma heavy chain (variable domain) and lambda light chain (constant domain). In view of the absence of circulating monoclonal Ig, this case supports the hypothesis that localized amyloid is formed by local plasmacytoid cells.

show abstract

Section: Discussionsupporting

confidence: 91%

Co-deposition of amyloidogenic immunoglobulin light and heavy chains in localized pulmonary amyloidosis

et al. 2005

View full text Add to dashboard Cite

show abstract

“…The 14-kDa protein band and its reaction with anti-kappa could indicate that the fibrils contain fragments of the constant region as observed earlier [8]. A cleavage with cyanogen bromide verified positions 1-4 and 5-12, when the sequencer was stopped.…”

Section: Resultssupporting

confidence: 73%

The amino acid sequence of an AL-protein, AL-KH, isolated from the heart of a patient with Waldenstroms macroglobulinemia and amyloidosis

Kjæraas

Husby

Sletten

2006

Amyloid

View full text Add to dashboard Cite

An AL-protein was isolated from the myocardium of a patient (KH) with Waldenstrom's macroglobulinemia. SDS-PAGE of the fraction revealed three major bands ranging from 14 to 30 kDa. Two of the major bands showed a positive PAS test for carbohydrate. The amino acid sequence was established for positions 1-92 and for positions 104-205, except for 150-187. According to the data, the AL-protein KH is derived from the kappa 1c germline gene.

show abstract

“…After separation in the Tris-Tricine system, proteins were transferred to a 0.2-m poly(vinylidene difluoride) membrane (Bio-Rad) and stained with 0.025% Coomassie blue R250 (without acetic acid). The Ͻ6.5-kDa protein band, which was reactive with A172 in Western blot analysis, was cut out and applied directly to an automatic protein sequencer (Applied Biosystems 477A) connected to a 120-A phenylthiohydantoin Analyzer (PerkinElmer) as described (15). In one case, sequencing also was performed directly on RP-HPLC-separated samples dried in a vacuum centrifuge.…”

Section: Methodsmentioning

confidence: 99%

Medin: An integral fragment of aortic smooth muscle cell-produced lactadherin forms the most common human amyloid

Häggqvist

Näslund

Sletten

et al. 1999

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

194

156

View full text Add to dashboard Cite

Aortic medial amyloid is a form of localized amyloid that occurs in virtually all individuals older than 60 years. The importance and impact of the amyloid deposits are unknown. In this study we have purified a 5.5-kDa aortic medial amyloid component, by size-exclusion chromatography and RP-HPLC, from three individuals, and we have shown by amino acid sequence analysis that the amyloid is derived from an integral proteolytic fragment of lactadherin. Lactadherin is a 364-aa glycoprotein, previously known to be expressed by mammary epithelial cells as a cell surface protein and secreted as part of the milk fat globule membrane. The multidomain protein has a C-terminal domain showing homology to blood coagulation factors V and VIII. We found that the main constituent of aortic medial amyloid is a 50-aa-long peptide, here called medin, that is positioned within the coagulation factor-like domain of lactadherin. Our result is supported by the specific labeling of aortic medial amyloid in light and electron microscopy with two rabbit antisera raised against two synthetic peptides corresponding to different parts of medin. By using in situ hybridization we have shown that lactadherin is expressed by aortic medial smooth muscle cells. Furthermore, one of the synthetic peptides forms amyloid-like fibrils in vitro. Lactadherin was not previously known to be an amyloid precursor protein or to be expressed in aortic tissue. The structure of lactadherin may implicate an important regulatory function in the aorta.

show abstract

Constant Region of a κ III Immunoglobulin Light Chain as a Major AL‐Amyloid Protein

Cited by 45 publications

References 37 publications

Co-deposition of amyloidogenic immunoglobulin light and heavy chains in localized pulmonary amyloidosis

Co-deposition of amyloidogenic immunoglobulin light and heavy chains in localized pulmonary amyloidosis

The amino acid sequence of an AL-protein, AL-KH, isolated from the heart of a patient with Waldenstroms macroglobulinemia and amyloidosis

Medin: An integral fragment of aortic smooth muscle cell-produced lactadherin forms the most common human amyloid

Contact Info

Product

Resources

About