SFEBES2025 Emerging Researcher and Plenary Orals Clinical Endocrinology Journal Foundation Best Abstract (Basic) (1 abstracts)
scRNAseq of orbital fat in thyroid eye disease reveals role of thyroid hormone signalling driving fibroblast function and identifies fibroblast-produced serum SPARC (osteonectin) as biomarker
Stephanie Hanna 1 , Emma Robinson 1 , Katie Boest Bjerg 1 , Alexandros Delimichalis 1 , Robert Andrews 1 , Ilaria Muller 2,3 , Ebony Smith 4 , Jadwiga Furmaniak 1 , Marian Ludgate 1 , Peter Taylor 1 , Catherine Rennie 5 , Dan Morris 4 , Anjana Haridas 4 , Vickie Lee 5 & Colin Dayan 1
1Cardiff University, Cardiff, United Kingdom. 2Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. 3Department of Endocrinology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. 4Cardiff and Vale University Health Board, Cardiff, United Kingdom. 5Imperial College & London North West University Healthcare NHS Trusts, London, United Kingdom
Background: A subset of patients with Graves’ disease (GD) develop thyroid eye disease (TED), where orbital fat proliferates, resulting in protrusion of the eyes, disfigurement and even blindness. Antibodies that trigger GD can also cause TED. However, there remains a paucity of information about whether thyroid hormones can drive pathological processes in the orbital fat fibroblasts and the secretion of pro-inflammatory mediators by the fibroblasts. Furthermore, there is an unmet need to identify biomarkers that predict development of TED.
Methods: We profiled cells obtained from orbital decompressions in patients with TED, using scRNAseq, and examined mediators in the serum from healthy controls and participants in the CIRTED, INDIGO and Immunological Determinants of Graves’ Disease studies.
Results: We found that fibroblasts were enriched for SLC16A2 (the T4/T3 transporter), DIO2 which catalyses conversion of T4 to T3, and THRA/B, the nuclear receptor for T3. In the serum we found that IGF1 was raised in subjects with thyroid disease but not further raised in those with TED. We wished to identify mediators from the fibroblasts released into the blood. We were particularly interested in SPARC (osteonectin) as highly produced by orbital fibroblasts in our scRNAseq analysis. Serum analysis identified that SPARC was significantly raised in people with thyroid disease compared to healthy controls. Furthermore, those with moderate to sight threatening TED had higher SPARC levels than those with thyroid disease alone or mild TED and their SPARC levels were positively correlated with FT3 and FT4.
Conclusion: Pathogenic processes in orbital fat are highly complex, involving TSHR, IGF1R (as targeted by teprotumumab) chemokine and cytokine signalling but also thyroid hormone signalling, resulting in elevated secretion of SPARC. This underscores the need to achieve euthyroidism to prevent development or progression of TED and suggests SPARC as a biomarker for the development of TED.
Volume 109
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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