Anakinra-Associated Systemic Amyloidosis.

Abstract

OBJECTIVE:

To describe a 41-year-old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin-1 receptor antagonist (IL-1Ra) protein, anakinra, since the age of 28, who presented with golf-ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation.

METHODS:

Clinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo-red staining and proteomic evaluation of microdissected Congo red-positive amyloid deposits by liquid chromatography-tandem mass spectrometry.

RESULTS:

The skin, stomach, and kidney biopsies all showed the presence of Congo red-positive amyloid deposits. Mass spectrometry-based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL-1Ra protein)-type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P-component) and the amyloidogenic IL-1Ra protein, which were present in Congo red-positive areas and absent in Congo red-negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL-1Ra (anakinra) and not endogenous wild-type IL-1Ra.

CONCLUSION:

This is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra).

• Authors: Sara Alehashemi, Surendra Dasari, Anvitha Metpally, Kat Uss, Leslie A Castelo-Soccio, Theo Heller, Peter Kellman, Marcus Y Chen, Mark Ahlman, Jeff Kim, Susannah Wargo, Douglas B Kuhns, Danielle Fink, Adriana de Jesus, Paul S Martin, Richard Chang, Jonathan Bolanos, Chyi-Chia Richard Lee, Samih H Nasr, Raphaela Goldbach-Mansky, Ellen McPhail
• Journal: Arthritis & rheumatology (Hoboken, N.J.) (Arthritis Rheumatol) (Jul 24 2023) ISSN: 2326-5205 [Electronic] United States
• PMID: 37488949 (Publication Type: Journal Article)
• Copyright: © 2023 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.