Association of increased eomesodermin, BCL6, and granzyme B expression with major clinical manifestations of Hashimoto’s thyroiditis – an observational study

ABSTRACT

Purpose

Studies of cytotoxic T cells and their respective lineage master regulators have been limited in Hashimoto’s thyroiditis (HT). It is unclear whether their transcriptomes are changed in HT patients and how these changes are associated with the thyroid damage, major clinical manifestations, and disease progression.

Methods

We explored the gene expression patterns of selected transcription factors [eomesodermin (EOMES), BACH2, BCL6, TCF1] and cytolytic molecules [granzyme B (GZMB)] in peripheral blood (PB) T cells of 10 healthy controls and 30 HT patients of various subtypes (hypothyroid, untreated HT; L-thyroxine (T4)-treated HT, and spontaneously euthyroid HT) using real-time quantitative PCR.

Results

EOMES (Mann–Whitney P = 0.044), GZMB (P = 0.028), and BCL6 mRNA (P = 0.001) were overrepresented in PB T cells from HT and showed levels varying by age, thyroid volume and disease severity. BCL6 transcripts were predominantly enriched in severely affected, hypothyroid cases, both on and off LT4. Increased EOMES RNA expression was associated with advancing age, lower thyroid volumes and higher peak adjusted TSH levels over the course of the disease. The body mass-adjusted, steady-state maintenance dose of LT4 increased with GZMB and BCL6 levels in PB T cells of hypothyroid cases, mostly postmenopausal women having long-standing, non-goitrous and atrophic disease form.

Conclusions

Our exploratory results suggest a role for GZMB, EOMES, and BCL6 in the context of HT, thyroid injury, and aggressive/advanced disease forms. Functions enriched within differentially expressed transcripts could be an important new target in understanding the pathogenesis of HT.

KEYWORDS:

• BCL-6
• EOMES
• Granzymes
• Hashimoto disease
• T-Lymphocytes

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by the Croatian Ministry of Science, Education and Sports (Grant No. 219-2190372-2068) and Josip Juraj Strossmayer University of Osijek (VIF2016MEFOS-37).