Purpose:
To identify biochemical inflammatory markers predicting presence or risk of developing thyroid eye disease (TED) in patients with Graves` disease (GD).
Methods:
Patients with GD (n = 100, 77 females) were included from the National Norwegian Registry of Organ Specific Diseases (ROAS). Serum samples were analysed for 92 different inflammatory biomarkers using proximity extension assay. Biomarker levels were compared between groups of patients with and without TED, and healthy subjects (n = 120).
Results:
TED was found in 36 of 100 GD patients. Significant (p < 0.05) differences in the levels of 52 inflammatory biomarkers were found when GD patients and healthy subjects were compared (42 elevated, 10 decreased). Out of the 42 elevated biomarkers, a significantly higher serum level of interleukin-6 (IL-6) (p = 0.022) and macrophage colony-stimulating factor (CSF-1) (p = 0.015) were found in patients with TED compared to patients without TED. Patients with severe TED also had significant elevation in serum level of Fms-related tyrosine kinase 3 ligand (Flt3L) (p = 0.009). Furthermore, fibroblast growth factor 21 (FGF-21), was significantly increased (p = 0.008) in patients with GD who had no signs of TED at baseline, but developed TED later.
Conclusion:
We demonstrate an immunologic fingerprint of GD, as serum levels of several inflammation related proteins were elevated, while others were decreased. Distinctly increased levels of IL-6, CSF-1, Flt3L, and FGF-21 were observed in TED, suggesting that these inflammatory proteins could be important in the pathogenesis, and therefore may be potentially new biomarkers.