Novel Type of Renal Amyloidosis Derived from Apolipoprotein-CII.
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.
Departments of Laboratory Medicine and Pathology.
Samih H
SH
Nasr
Health Sciences Research, and.
Surendra
S
Dasari
Departments of Laboratory Medicine and Pathology.
Linda
L
Hasadsri
Departments of Laboratory Medicine and Pathology.
Jason D
JD
Theis
Departments of Laboratory Medicine and Pathology.
Julie A
JA
Vrana
Internal Medicine, Mayo Clinic, Rochester, Minnesota; and.
Morie A
MA
Gertz
Departments of Laboratory Medicine and Pathology.
Prasuna
P
Muppa
Health Sciences Research, and.
Michael T
MT
Zimmermann
Departments of Laboratory Medicine and Pathology.
Karen L
KL
Grogg
Departments of Laboratory Medicine and Pathology.|Internal Medicine, Mayo Clinic, Rochester, Minnesota; and.
Angela
A
Dispenzieri
Departments of Laboratory Medicine and Pathology.
Sanjeev
S
Sethi
Departments of Laboratory Medicine and Pathology.
W Edward
WE
Highsmith
Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Giampaolo
G
Merlini
Internal Medicine, Mayo Clinic, Rochester, Minnesota; and.
Nelson
N
Leung
Departments of Laboratory Medicine and Pathology, kurtin.paul@mayo.edu.
Paul J
PJ
Kurtin
D000686:Amyloidosis / Q000145:classification / Q000209:etiology*; D053304:Apolipoprotein C-II / Q000502:physiology*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000145:classification / Q000209:etiology*; D008875:Middle Aged
D053304:Apolipoprotein C-II
amyloidosis; apolipoprotein C-II; hereditary amyloidosis; renal amyloid