Cardiff-led team links serum SPARC to active thyroid eye disease in four clinical cohorts
Orbital fat fibroblasts express SPARC, and its serum level was highest in moderate-to-sight-threatening disease and fell by week 48 as clinical activity scores dropped.
A team from Cardiff University, the University of Birmingham and partner centres reported in Frontiers in Endocrinology on 12 November 2026 (doi.org) that serum SPARC is elevated in thyroid eye disease (TED). The work combined single-cell RNA sequencing of orbital fat from four people with TED with ELISA measurements of serum proteins in three separate cohorts, plus one independent validation cohort frontiersin.org
doi.orgfrontiersin.orgOpen source ↗.
TED is an extrathyroidal manifestation of Graves' disease. Orbital inflammation, overproduction of extracellular matrix and expansion of adipose tissue cause proptosis, disfigurement and sight loss. The authors note that reliable serum biomarkers of active disease are still lacking, and that little is known about how thyroid hormones act on orbital fat fibroblasts.
Single-cell profile of orbital fat
Orbital fat was obtained during decompression surgery. Single-cell sequencing identified orbital fibroblast subsets expressing thyroid hormone receptors (THRA, THRB), the T4/T3 transporter SLC16A2, DIO2, IGF1R and extracellular matrix proteins, including SPARC.
In additional orbital fat samples, immunofluorescence showed heterogeneous SPARC expression by fibroblasts in both control and TED tissue frontiersin.org
doi.orgfrontiersin.orgOpen source ↗.
Serum SPARC across cohorts
Serum SPARC, fibronectin, IGF-1 and other proteins were measured in healthy controls and in participants with thyroid disease, stratified by TED severity. SPARC was significantly higher in people with thyroid disease than in healthy controls. It was highest in those with moderate-to-sight-threatening TED in all three primary cohorts, and the finding was confirmed in the validation cohort.
In moderate-to-sight-threatening TED, serum SPARC correlated positively with FT3 and negatively with TSH. SPARC and IGF-1 correlated positively regardless of TED status. During follow-up, serum SPARC declined significantly by week 48 as clinical activity scores fell.
The authors suggest SPARC as a candidate biomarker of active TED. They also describe the data as evidence linking circulating T3 to orbital fibrotic processes, which in their view supports strict thyroid function control in TED management frontiersin.org
doi.orgfrontiersin.orgOpen source ↗. The study is observational and does not test SPARC as a diagnostic tool in practice.
