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J Am Soc Nephrol. 2017 Feb;28(2):439-445. doi: 10.1681/ASN.2015111228. Epub 2016 Jun 13.

Novel Type of Renal Amyloidosis Derived from Apolipoprotein-CII.

Author information

1
Departments of Laboratory Medicine and Pathology.
2
Health Sciences Research, and.
3
Internal Medicine, Mayo Clinic, Rochester, Minnesota; and.
4
Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy.
5
Departments of Laboratory Medicine and Pathology, kurtin.paul@mayo.edu.

Abstract

Amyloidosis is characterized by extracellular deposition of misfolded proteins as insoluble fibrils. Most renal amyloidosis cases are Ig light chain, AA, or leukocyte chemotactic factor 2 amyloidosis, but rare hereditary forms can also involve the kidneys. Here, we describe the case of a 61-year-old woman who presented with nephrotic syndrome and renal impairment. Examination of the renal biopsy specimen revealed amyloidosis with predominant involvement of glomeruli and medullary interstitium. Proteomic analysis of Congo red-positive deposits detected large amounts of the Apo-CII protein. DNA sequencing of the APOC2 gene in the patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. We also detected the mutant peptide in the proband's renal amyloid deposits. Using proteomics, we identified seven additional elderly patients with Apo-CII-rich amyloid deposits, all of whom had kidney involvement and histologically exhibited nodular glomerular involvement. Although prior in vitro studies have shown that Apo-CII can form amyloid fibrils and that certain mutations in this protein promote amyloid fibrillogenesis, there are no reports of this type of amyloidosis in humans. We propose that this study reveals a new form of hereditary amyloidosis (AApoCII) that is derived from the Apo-CII protein and appears to manifest in the elderly and preferentially affect the kidneys.

KEYWORDS:

amyloidosis; apolipoprotein C-II; hereditary amyloidosis; renal amyloid

PMID:
27297947
PMCID:
PMC5280007
DOI:
10.1681/ASN.2015111228
[Indexed for MEDLINE]
Free PMC Article

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