Abstract
Purpose: :
Fibrocytes are circulating bone marrow-derived stem cells that traffic to sites of inflammation and fibrosis. We have demonstrated that patients with Graves’ disease (GD) and TAO have an increased abundance of circulating fibrocytes in a cross-sectional cohort. These cells express high levels of thyrotropin receptor (TSHR), a self-antigen central to GD pathogenesis. Here we determine the impact of disease duration on fibrocyte frequency.
Methods: :
A clinical cohort of 33 subjects with long-standing or recently diagnosed TAO and 19 healthy controls were recruited. Peripheral blood was analyzed by flow cytometry to identify and characterize fibrocytes, which were defined as CD45+/Col1+ monocytes. Fibrocyte index was calculated as percentage of gated monocytes expressing both CD45 and Col1.
Results: :
Cross-sectional data showed a fibrocyte index of 33.8% in patients with TAO compared to 6.9% in controls. Fibrocytes from patients with TAO display TSHR and CD40 on 67.8% and 35.7% of fibrocytes, respectively. Longitudinal data from 2 patients with TAO shows that the fibrocyte index exhibited a decrease from 50% to 9.3% and 63% to 4.9%, respectively, but expression of TSHR and CD40 remained constant.
Conclusions: :
We report that the abundance of fibrocytes directly identified using a CD45+ flow cytometric technique is increased in individuals with TAO. Moreover, preliminary evidence is presented for a time-dependent decrease in the fibrocyte index in patients with TAO. Thus the fibrocyte index may be a clinically useful biomarker for assessing patients with GD.
Keywords: autoimmune disease • flow cytometry • cytokines/chemokines