Functional human TSHβ splice variant produced by plasma cell may be involved in the immunologic injury of thyroid in the patient with Hashimoto's thyroiditis

Abstract

Hashimoto's Thyroiditis (HT) is the most common cause of hypothyroidism in areas of the world where iodine levels are sufficient. However, the pathogenesis of HT has not been completely elucidated. The first functional human TSHβ splice variant was supposed to be involved in the pathology of Hashimoto's thyroiditis. The question remains as to which kind of intrathyroid cells expresses functional TSHβ splice variant and whether there are expression variations of functional TSHβ splice variant in the injured thyroid of patient with HT. For the answer to this question, immune-injured thyroids were obtained from 30 patients with HT. Localization study of functional TSHβ splice variant in injured thyroid was done by immunofluorescence double staining. Transcription and translation level of functional TSHβ splice variant were detected by using qRT-PCR and semi-quantitative immunohistochemistry method, respectively. The correlation between expression level of functional TSHβ splice variant and degree of thyroid follicles damage was assessed. It was firstly identified that functional TSHβ splice variant was predominately expressed by plasma cells infiltrated around follicles and germinal center in injured thyroid of patient with HT. Of particular interest, the TSHβ splice variant was expressed at significantly higher levels in the thyroid tissues of patients with HT than that in the normal thyroid tissues, furthermore, expression level of TSHβ splice variant was positive related with the degree of follicles damage in thyroid of patient with HT. These findings defined the immune-derived functional TSHβ splice variant that resided in the thyroid of patient with HT, which exerted the unique effects on the pathogenesis of HT, meanwhile, we considered these findings to have significant implications for understanding immune-endocrine interactions in a number of ways.

Keywords: Hashimoto's thyroiditis; Human; Plasma cell; TSHβ splice variant; Thyroid.