1. A Novel Truncated Form of Serum Amyloid A in Kawasaki Disease.
- Author
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Whitin, John C, Yu, Tom To-Sang, Ling, Xuefeng Bruce, Kanegaye, John T, Burns, Jane C, and Cohen, Harvey J
- Subjects
Humans ,Mucocutaneous Lymph Node Syndrome ,Acute-Phase Reaction ,Fever ,Serum Amyloid A Protein ,Protein Isoforms ,Codon ,Nonsense ,Diagnosis ,Differential ,Spectrometry ,Mass ,Matrix-Assisted Laser Desorption-Ionization ,Case-Control Studies ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Coronary Artery Disease ,Biomarkers ,Codon ,Nonsense ,Diagnosis ,Differential ,Spectrometry ,Mass ,Matrix-Assisted Laser Desorption-Ionization ,Preschool ,General Science & Technology - Abstract
BackgroundKawasaki disease (KD) is an acute vasculitis in children that can cause coronary artery abnormalities. Its diagnosis is challenging, and many cytokines, chemokines, acute phase reactants, and growth factors have failed evaluation as specific biomarkers to distinguish KD from other febrile illnesses. We performed protein profiling, comparing plasma from children with KD with febrile control (FC) subjects to determine if there were specific proteins or peptides that could distinguish the two clinical states.Materials and methodsPlasma from three independent cohorts from the blood of 68 KD and 61 FC subjects was fractionated by anion exchange chromatography, followed by surface-enhanced laser desorption ionization (SELDI) mass spectrometry of the fractions. The mass spectra of KD and FC plasma samples were analyzed for peaks that were statistically significantly different.ResultsA mass spectrometry peak with a mass of 7,860 Da had high intensity in acute KD subjects compared to subacute KD (p = 0.0003) and FC (p = 7.9 x 10-10) subjects. We identified this peak as a novel truncated form of serum amyloid A with N-terminal at Lys-34 of the circulating form and validated its identity using a hybrid mass spectrum immunoassay technique. The truncated form of serum amyloid A was present in plasma of KD subjects when blood was collected in tubes containing protease inhibitors. This peak disappeared when the patients were examined after their symptoms resolved. Intensities of this peptide did not correlate with KD-associated laboratory values or with other mass spectrum peaks from the plasma of these KD subjects.ConclusionsUsing SELDI mass spectrometry, we have discovered a novel truncated form of serum amyloid A that is elevated in the plasma of KD when compared with FC subjects. Future studies will evaluate its relevance as a diagnostic biomarker and its potential role in the pathophysiology of KD.
- Published
- 2016