Conference Coverage

Probe-Based TTR Stability Immunoassay Distinguishes ATTR-CM in 47-Patient Study

Edited by:
Brian McCurdy

Key Highlights

  • The study compared serum samples from 20 patients with ATTR-CM and 27 age- and sex-matched cardiovascular controls.
  • The TTR tetramer stability index was significantly lower in ATTR-CM, while total circulating TTR concentrations did not differ significantly.
  • A subgroup analysis found lower stability in patients with NYHA class I or II ATTR-CM.

A novel probe-based immunoassay identified lower transthyretin (TTR) tetramer stability in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) than in cardiovascular controls, including among patients with mild symptoms. Researchers from Kobe, Japan, are presenting the findings at the 2026 American Heart Association.

The investigators developed the assay to address difficulties in clinically assessing TTR tetramer stability. Building on findings that unstable TTR variants have lower T4-binding capacity, they designed a small-molecule probe targeting the T4-binding pocket and evaluated its ability to measure stability.

Serum samples came from 20 patients with ATTR-CM, 18 with wild-type TTR and 2 with the A36D variant, and 27 age- and sex-matched patients with cardiovascular disease. Controls had no evidence of cardiac hypertrophy or carpal tunnel syndrome. A subgroup analysis included 16 patients with mildly symptomatic ATTR-CM classified as New York Heart Association (NYHA) class I or II and 22 controls.

The assay captured tetrameric TTR using the probe and detected it with an anti-TTR antibody. We normalized probe-binding signals to each sample’s total TTR concentration to generate a tetramer stability index. All measurements used a fully automated immunoassay platform.

Study Findings

In proof-of-concept experiments with recombinant proteins, probe-binding signals were lower for the unstable TTR variants V30M, V122I, and L55P than for wild-type TTR and the stable T119M variant. In clinical samples, the stability index was significantly lower in patients with ATTR-CM than in controls (Mann-Whitney U test, P < .001). Receiver operating characteristic analysis yielded an area under the curve of 0.819.

By comparison, total circulating TTR measured with a conventional antibody-based immunoassay did not differ significantly between groups (P = .635). The mildly symptomatic ATTR-CM subgroup also demonstrated significantly lower tetramer stability than controls, without a significant difference in total TTR concentrations.

Clinical Implications

The authors suggest that reduced interaction between TTR and the probe indicates decreased tetramer stability in ATTR-CM. They interpreted the findings as supporting the potential diagnostic utility of assessing stability, including in patients with mild symptoms.

Expert Commentary

“These results suggest that reduced TTR tetramer stability is a characteristic feature of ATTR CM, including in patients with mild symptoms, and support its potential diagnostic utility in clinical settings,” the researchers concluded.

Reference

Kobayashi Y, Nagao M, Iino T, et al. Development of a novel probe based immunoassay to assess transthyretin tetramer stability in patients with ATTR CM. Abstract MDP2075. Presented at: American Heart Association Scientific Sessions 2026; November 9, 2026.