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systemic amyloidosis

Wednesday 6 February 2008

systemic amyloidoses


- systemic amyloidosis: deposits within vessel walls

Definition: The amyloidoses represent a group of acquired or inherited disorders characterized by the pathologic deposition of wild-type or mutated proteins as fibrils within the kidney or other vital organs/tissues throughout the body.

Since at lease 25 biochemically distinct amyloidogenic
molecules have been identified, of which 9 are known to form renal amyloid deposits, it is essential for therapeutic and prognostic purposes that the kind of amyloid be correctly

Heretofore, the diagnosish as been dependent principally upon immunohistochemistry (and ancillary clinical data); however, limitations in antibody reactivity and specificity have resulted in misinterpretation, particularly when differentiating primary or
light chain-associated (AL) from secondary or serum amyloid A protein-associated (AA) amyloidosis.

To ascertain if an individual has AL, AA, or some other kind of amyloid disease, the green birefringent material contained in biopsy-derived specimens should be extracted and analyzed chemically by tandem mass spectrometry (MS/MS) to gain this information using sections cut from formalin-fixed, paraffin-embedded tissue biopsies
or subcutaneous fat aspirates scraped from glass microscopic slides.

Given the fact that the clinical management and ultimate fate of patients with amyloidosis is dependent on the amyloid type, it is crucial that the nature of the fibrillar protein be established unequivocally in order to avoid inappropriate and costly therapy that can have dire and possible legal consequences.


Precursor Protein Wild-Type (WT)/Mutated (MUT) Type of Amyloid
Light Chain (kappa or lambda) WT AL
Serum Amyloid A 1/2 (SAA1/2) WT AA
Serum Amyloid A 4 (SAA4) MUT AA
Apolipoprotein A-I (Apo A-I) MUT AApo A-I
Apolipoprotein A-II (Apo A-II) MUT AApo A-II
Fibrinogen (FIB) MUT AFIB
Lysosyme (LYS) MUT ALYS
Transthyretin (TTR) MUT ATTR
Leucocyte Cell-Derived Chemotaxin 2 (LECT 2) WT ALECT2


- Murphy CL, Eulitz M, Hrncic R, Sletten K, Westermark P, Williams T, Macy SD, Wooliver C, Wall J, Weiss DT, and Solomon A. Chemical typing of amyloid protein contained in formalin- fixed paraffin-embedded biopsy specimens. Am. J. Clin. Pathol. 116, 135-142, 2001.

- Solomon A, Weiss DT, and Herrera GA. Renal diseases associated with multiple myeloma and related plasma cell dyscrasias. In Biology and Management of Multiple Myeloma. Berenson, J.R. Ed. Humana Press, New Jersey, 2004; pp. 281-302.

- Murphy CL, Wang S, Williams T, Weiss DT, and Solomon A. Characterization of systemic amyloid deposits by mass spectrometry. Methods Enzymol. 412,48-62, 2006.

- Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003 Aug 7;349(6):583-96. PMID: 12904524

- Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997 Sep 25;337(13):898-909. PMID: 9302305

- Glenner GG. Amyloid deposits and amyloidosis: the beta-fibrilloses (second of two parts). N Engl J Med. 1980 Jun 12;302(24):1333-43. PMID: 6990257

- Glenner GG.Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts). N Engl J Med. 1980 Jun 5;302(23):1283-92. PMID: 6154243