Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration

Abstract

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.

Atypical presentation of localized insulin‐derived amyloidosis as protruding brownish skin tumours

“…It was reported that in patients with LIDA, there was an equal distribution of Type 1 and Type 2 diabetes . LIDA predominantly affects male patients, with a sex ratio of about 2 : 1 . The average age of male and female patients with LIDA in the study was similar (59.8 and 56.5 years, respectively) …”

“…LIDA predominantly affects male patients, with a sex ratio of about 2 : 1 . The average age of male and female patients with LIDA in the study was similar (59.8 and 56.5 years, respectively) …”

Absolute Quantification of Amyloid Propagons by Digital Microfluidics

“…In addition, d-AQuA might be of practical use for the detection of even the smallest traces of insulin aggregates that cannot be detected with existing analytical methods in biopharmaceutical preparations of insulin products used for therapy in diabetes patients 47−49 and may lead to an immune response in patients after subcutaneous injection. 49 Our technology also holds the potential to be used for rapid, ultrasensitive and highly parallel preclinical and clinical diagnosis through the detection of early pathological propagons in protein misfolding and aggregation (PMA) diseases for personalized medicine. In particular, a small-volume, single-use disposable chip with the ability to diagnose accurately PMA diseases from body fluids holds great promise for novel automated diagnostic approaches.…”

The amyloid interactome: Exploring protein aggregation

“…The subsequent construction of the network incorporated only well-characterized in vivo amyloidogenic proteins, published by Sipe et al [2], excluding Enfurvitide an anti-retroviral peptide drug [43], as well as Immunoglobulin Light and Heavy Chains. In the case of Immunoglobulin chains (e.g.…”