The establishment of specific reference intervals for serum transthyretin tetramer, misfolded proteins, and protein misfolding rate and its application in evaluating transthyretin amyloidosis patients.

BACKGROUND

To accurately assess disease risk, specific reference intervals for transthyretin (TTR) tetramers, misfolded proteins, and protein misfolding rates are essential. This study aimed to establish reference intervals using a robust and traceable ultrahigh performance liquid chromatography (UPLC) method and to evaluate the distribution of these biomarkers in patients with transthyretin amyloidosis (ATTR).

METHODS

Serum samples from 331 healthy Chinese individuals were included. Participants were stratified into two age groups: <60 years and ≥ 60 years. The reference intervals were determined following the Clinical and Laboratory Standards Institute (CLSI) EP28-A3.

RESULTS

The established reference intervals for TTR tetramers, misfolded proteins, and protein misfolding rates revealed significant age- and sex-specific variations. In the < 60 years age group, the TTR tetramer reference intervals were 3.01-6.30 μmol/L for males and 2.62-5.39 μmol/L for females. Corresponding reference intervals for misfolded proteins were 0.24-1.43 μmol/L for males and 0.33-1.39 μmol/L for females, with protein misfolding rate upper limits of 26.32 % and 27.47 %, respectively. In the ≥ 60 years age group, TTR tetramer reference intervals from 2.56-5.48 μmol/L for males and 2.36-5.10 μmol/L for females. Misfolded protein reference intervals were 0.28-2.03 μmol/L for males and 0.29-1.59 μmol/L for females, while protein misfolding rate upper limits were 33.69 % for males and 30.64 % for females.

CONCLUSIONS

This study successfully established detailed, age- and sex-specific reference intervals for TTR tetramers, misfolded proteins, and protein misfolding rates, providing valuable references for clinical practice and further investigations into disease risk associated with TTR biomarkers.