Individuals with hereditary transthyretin amyloidosis (hATTR) exhibit comprehensive plasma protein profiles at various stages of their disease, according to findings from a study conducted at the Peking Union Medical College Hospital in Beijing, China, and published in the journal Expert Review of Proteomics.

hATTR comprises a group of progressive, incurable protein-folding diseases in which deposits of insoluble protein fibrils are found in the extracellular matrix of such target organs as the heart and the nerves. There have been more than 40 amyloidogenic proteins verified, with transthyretin (TTR) known to be a typical protein. More than
140 mutations have been revealed in the exons of the TTR gene, which is on chromosome 18q12.1.

Diagnosis of hATTR has been rendered difficult because of the lack of ATTR-specific biomarkers, limited known pathogenic mechanisms, and major dependence on biopsy of the affected organ.

The researchers sought to utilize data-independent acquisition-based quantitative proteomics (DIA) to determine plasma protein profiles in Chinese patients with hATTR. Additionally, they evaluated differential plasma proteins in 3 different phenotypes of the disease—(1) neuropathy: hATTR-PN; (2) cardiopathy: hATTR-CM; (3) neuropathy and cardiopathy: hATTR-MIX—which were then compared with healthy controls.

The results of proteomic and bioinformatic analyses were combined to identify candidate molecules, in an effort to improve the screening of potential biomarkers and better understand the pathogenic mechanisms involved in hATTR. The investigators used the STRING proteomic database to search for protein-protein interactions.

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Serum samples were obtained from 18 untreated patients with hATTR—6 with hATTR-PN, 5 with hATTR-CM, and 7 with hATTR-MIX—and 20 healthy controls. The controls were matched with the patients based on age, gender, and race. The mean patient age was 49.7±2.3 years. Of the 18 patients, 13 were male and all were of Asian ethnicity.

Based on STRING analysis of hATTR subtypes, 30 differentially expressed proteins (DEPs) were reported between the hATTR-PN group and the control group, which were enriched in the estrogen signaling pathway and cell adhesion molecules . A total of 22 DEPs were observed between patients with hATTR-CM and controls, which were enriched in peroxisome proliferator-activated receptor (PPAR) signaling, cell adhesion, and extracellular matrix (ECM)-receptor interactions. There were a total of 62 DEPs observed between the hATTR-MIX arm and the control arm, which were divided into 2 clusters, based on experimental determination or text-mining.

“These significant variations in the level of plasma protein related to [hATTR] phenotype provided important information to identify potential biomarkers for neuropathy and cardiopathy of . . . patients [with hATTR],” the researchers explained. “[O]ur novel findings may provide new therapeutic targets for . . . patients [with hATTR] for future research,” they concluded.


He S, He XY, Pan RK, et al. Data-independent acquisition mass spectrometry reveals comprehensive plasma protein profiles in the natural history of patients with hereditary transthyretin amyloidosis (ATTRv). Expert Rev Proteomics. Published online April 6, 2023. doi:10.1080/14789450.2023.2195096