Details

Autor(en) / Beteiligte

• Wang, Shuang
• Guan, Liping
• Sun, Yang
• Cui, Li
• Guo, Shigang
• Wang, Mengdie
• Liu, Yu
• Cui, Xueting
• Zhao, Furong
• Zhang, Yanjie
• Cao, Yunfeng

Titel

An ultra performance liquid chromatography method for transthyretin variants screening and heart failure assisting diagnosis

Ist Teil von

• Clinica chimica acta, 2024-01, Vol.553, p.117709-117709, Article 117709

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •An UPLC-ion exchange column method in suit quantification of human TTR tetramer by A2 binding was developed.•UPLC method simultaneously quantification and identification of variants TTR, saving on time and cost.•This UPLC method was applied for clinical samples analysis with ATTR.•TTR tetramer showed highly correlation with NT-proBNP. Transthyretin (TTR) gene mutations are associated with hereditary amyloidosis (ATTR) caused by mutant TTR protein dissociation, misfolding, aggregation, and insoluble fibrils deposition. Herein, we reported a chromatographic approach for quantification and identification of TTR tetramer in human blood serum by ultra performance liquid chromatography (UPLC). TTR proteins and serum were incubated with a fluorescent TTR tetramer sensor (A2). The A2 sensor specifically reacted with tetrameric TTR and released stoichiometric fluorescence that was detected by fluorescence detector coupled to UPLC. The external standard was used for quantification, the chromatographic peak parameters were used to identification certain mutation types. UPLC correctly distinguished 18 types of mutant TTR proteins from wild type. The results were consistent with follow-up analysis of two ATTR patients’ blood serum samples. In addition, the tetrameric TTR of 30 heart failure (HF) patients showed strongly correlation (r = −0.63, p < 0.00) with NT-proBNP, a HF clinical biomarker. UPLC method has sufficient accuracy to eliminate the necessity of sequencing for certain types of TTR mutations and allows for facile initial screening of ATTR amyloidosis patients, carriers, and healthy individuals for time-saving and economical purposes. TTR tetramer may serve as a diagnostic biomarker to evaluate the risk of HF diseases.