Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration.
Protein and peptide drugs administered subcutaneously, such as insulin can be amyloidogenic and result in localized amyloid deposits at the sites of medication injections. These iatrogenic amyloidoses typically present as a localized subcutaneous nodule or skin reaction at the site of administration, and often pose diagnostic challenges. We have analyzed the amyloid proteome in 52 cases of insulin and enfuvirtide associated amyloidosis using laser microdissection/tandem mass spectrometry. We show that the deposits are composed of the drug, as well as other amyloid precursor proteins such as apolipoproteins A-I, A-IV, E and serum amyloid protein. Mass spectrometry-based amyloid sub-typing allows for accurate amyloid diagnosis with resultant therapeutic and prognostic implications. This insight into the amyloid proteome in drug-induced amyloidosis may help further understand pathogenesis of amyloid fibril formation.
Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN , USA .
Anita
A
D'Souza
Jason D
JD
Theis
Julie A
JA
Vrana
Ahmet
A
Dogan
D000328:Adult; D000368:Aged; D000682:Amyloid / Q000378:metabolism; D058227:Amyloidogenic Proteins / Q000378:metabolism; D000686:Amyloidosis / Q000139:chemically induced* / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects*; D006801:Humans; D007328:Insulin / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects*; D053719:Tandem Mass Spectrometry
D000682:Amyloid; D058227:Amyloidogenic Proteins; D016632:Apolipoprotein A-I; D015700:HIV Envelope Protein gp41; D007328:Insulin; D010446:Peptide Fragments; D000077560:Enfuvirtide
Drug-induced amyloid; iatrogenic; pharmaceutical amyloidosis