Proteomic analysis of highly prevalent amyloid A amyloidosis endemic to endangered island foxes

• Published in: PloS one 2014-11, Vol.9 (11), p.e113765-e113765
• Main Authors: Gaffney, Patricia M, Imai, Denise M, Clifford, Deana L, Ghassemian, Majid, Sasik, Roman, Chang, Aaron N, O'Brien, Timothy D, Coppinger, Judith, Trejo, Margarita, Masliah, Eliezer, Munson, Linda, Sigurdson, Christina
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Amyloid; Amyloidosis; Amyloidosis - epidemiology; Amyloidosis - metabolism; Amyloidosis - pathology; Amyloidosis - veterinary; Animals; Apolipoprotein A; Apolipoproteins; Binding sites; Biology and Life Sciences; Blood Vessels - chemistry; Blood Vessels - pathology; California - epidemiology; Carnivores; Complement component C3; Complement component C4; Departments; Disease; Endangered & extinct species; Endangered Species; Female; Fibrils; Fibrinogen; Foxes; Health risks; Immunology; Inflammatory diseases; Islands; Kidney - chemistry; Kidney - pathology; Kidneys; Laboratories; Male; Mass spectrometry; Mass spectroscopy; Medicine and Health Sciences; Molecular Sequence Data; Mouth - chemistry; Mouth - pathology; Mutation; Neurosciences; Oral cavity; Pathology; Peptides; Population genetics; Prevalence; Proteins; Proteomics; Reproductive Isolation; Risk analysis; Risk factors; Serum Amyloid A Protein - analysis; Serum Amyloid A Protein - ultrastructure; Spleen; Spleen - chemistry; Spleen - pathology; Urocyon littoralis santacruzae; Veterinary medicine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113765

Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤ 0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins.