Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis.

Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis. Research Abstract Details 

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Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis. Abstract Text:

Stina Enqvist,Knut Sletten,Fred J Stevens,Ulf Hellman,Per Westermark,

BACKGROUND: Amyloid is insoluble aggregated proteins deposited in the extra cellular space. About 25 different proteins are known to form amyloid in vivo and are associated with severe diseases such as Alzheime?s disease, prion diseases and type-2 diabetes. Light chain (AL) -amyloidosis is unique among amyloid diseases in that the fibril protein, a monoclonal immunoglobulin light chain, varies between individuals and that no two AL-proteins with identical primary structures have been described to date. The variability in tissue distribution of amyloid deposits is considerably larger in systemic AL-amyloidosis than in any other form of amyloidosis. The reason for this variation is believed to be based on the differences in properties of the amyloidogenic immunoglobulin light chain. However, there is presently no known relationship between the structure of an AL-protein and tissue distribution. METHODOLOGY/PRINCIPAL FINDINGS: We compared the pattern of amyloid deposition in four individuals with amyloid protein derived from variable light chain gene O18-O8, the source of a high proportion of amyloidogenic light chains, and in whom all or most of the fibril protein had been determined by amino acid sequencing. In spite of great similarities between the structures of the proteins, there was a pronounced variability in deposition pattern. We also compared the tissue distribution in these four individuals with that of four other patients with AL-amyloid derived from the L2-L16 gene. Although the interindividual variations were pronounced, liver and kidney involvement was much more evident in the latter four. CONCLUSIONS/SIGNIFICANCE: We conclude that although the use of a specific gene influences the tissue distribution of amyloid, each light chain exhibits one or more determinants of organ-specificity, which originate from somatic mutations and post-translational modifications. Eventual identification of such determinants could lead to improved treatment of patients with AL amyloidosis.

Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis. Publishing Authors By Initials

S Enqvist,K Sletten,FJ Stevens,U Hellman,P Westermark,

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Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: PLoS ONE

VOLUME: 2

Page Numbers: e981

Journal Abbreviation: PLoS ONE

ISSN: 1932-6203

DAY: 3

MONTH: 10

YEAR: 2007

Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis. Information

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LANGUAGE: eng

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AFFILIATION: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Country: United States

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