Dysregulated Proteins in Plasma Distinguishing Loeys-Dietz Syndrome from Other Heritable Thoracic Aortic Disease - An Explorative Study.

Objectives

Thoracic aortic aneurysms (TAA) are often found in younger individuals and approximately 20% may be associated with heritable thoracic aortic disease (HTAD). There are some data on genomic biomarkers reflecting inflammation and extracellular matrix remodeling in HTAD. However, data that accurately reflect the corresponding protein changes are scarce. Our aim was to quantify proteins by using targeted proteomics in HTAD patients versus healthy controls, to better understand the underlying pathophysiology.

Methods

Patients with Loeys-Dietz syndrome (LDS, n = 8), Marfan syndrome (MFS, n = 11), and familial thoracic aortic aneurysm 6, i.e. actin alpha 2 (ACTA2, n = 7) pathogenic variants were recruited at our outpatient clinic. For comparison, blood samples were drawn from 16 healthy controls. Plasma samples were analyzed by targeted proteome analysis of 276 proteins using immunoaffinity proteomics.

Results

Whereas Oncostatin M and Pentraxin 3 levels appeared generally higher in HTAD patients, after adjusting for several confounders, significantly higher levels for these markers as well as TNF Receptor Superfamily Member 9 (TNFRSF9), Granulysin (GNLY), CD5, Vasorin and Glycoprotein 1b-α (GP1BA) were only observed in LDS patients compared to healthy controls. Levels of TNFRSF9, GNLY, GP1BA and CD5 correlated positively with Th17 and platelet counts.

Conclusions

This discovery study suggest that LDS could represent a particular inflammatory subgroup of HTAD patients potentially reflecting the involvement of Th17 and platelet related mechanisms in the progression of TAA. Larger studies are needed to evaluate if the identified proteins could be used as biomarkers in these patients.