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. 2022 Jan 13;11(2):404.
doi: 10.3390/jcm11020404.

A Tear Metabolomic Profile Showing Increased Ornithine Decarboxylase Activity and Spermine Synthesis in Thyroid-Associated Orbitopathy

Benjamin Billiet  1 , Juan Manuel Chao de la Barca  2   3 , Marc Ferré  3 , Jeanne Muller  1 , Anaïs Vautier  1 , Sophie Assad  1 , Odile Blanchet  4 , Lydie Tessier  2 , Céline Wetterwald  2 , Justine Faure  2 , Geoffrey Urbanski  3   5 , Gilles Simard  2 , Delphine Mirebeau-Prunier  2   3 , Patrice Rodien  3   6 , Philippe Gohier  1 , Pascal Reynier  2   3
Affiliations

A Tear Metabolomic Profile Showing Increased Ornithine Decarboxylase Activity and Spermine Synthesis in Thyroid-Associated Orbitopathy

Benjamin Billiet et al. J Clin Med. .

Abstract

About half of patients with Graves' disease develop an orbitopathy related to an inflammatory expansion of the periorbital adipose tissue and muscles. We used a targeted metabolomic approach measuring 188 metabolites by mass spectrometry to compare the metabolic composition of tears in patients with active (n = 21) versus inactive (n = 24) thyroid-associated orbitopathy. Among the 44 metabolites accurately measured, 8 showed a significant alteration of their concentrations between the two groups. Two short-chain acylcarnitines, propionylcarnitine and butyrylcarnitine, and spermine showed increased concentrations in the tears of patients with active orbitopathy, whereas ornithine, glycine, serine, citrulline and histidine showed decreased concentrations in this group. In addition, the ratio putrescine/ornithine, representing the activity of ornithine decarboxylase, was significantly increased in patients with active compared to inactive orbitopathy (p = 0.0011, fold change 3.75). The specificity of this candidate biomarker was maintained when compared to a control group with unclassified dry eye disease. Our results suggest that the stimulation of ornithine decarboxylase by TSH receptor autoantibodies in orbital fibroblasts could lead to increased synthesis of spermine, through the increased activity of ornithine decarboxylase, that may contribute to periorbital expansion in Graves' ophthalmopathy.

Keywords: Graves’ ophthalmopathy; metabolomics; ornithine decarboxylase; spermine; thyroid-associated orbitopathy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pathophysiological model suggested by the tear metabolic signature obtained in active versus inactive TAO.
See this image and copyright information in PMC

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