Not Only Follicular Helper T‐Cells but Also Peripheral Helper T‐Cells Expanded Correlate With Disease Severity and B‐Cell Differentiation in Graves’ Disease

Objective To study the expression of peripheral helper T (Tph)‐cells in the blood and thyroid of Graves’ disease (GD) patients and their correlation with B‐cells and clinical indicators. Methods A total of 25 cases of newly diagnosed GD and 25 cases of healthy controls were recruited. Peripheral blood mononuclear cells were isolated. The frequency and proliferative activity of follicular helper T (Tfh)‐cells, Tph cells, and B‐cells were detected by flow cytometry. Thyroid tissues of 4 patients with GD and 4 normal thyroid tissues were selected for multiple immunofluorescence staining. The number of Tfh cells and Tph cells in the thyroid tissue was observed. Results Tph and Tfh cells were significantly increased in the blood and thyroid tissue of GD patients compared with healthy controls. Both cells were positively correlated with the proliferative activity of B‐cells. The proportion of Tph cells correlated with serum TT4 ( r = 0.501) and TR‐Ab ( r = 0.472) levels. Tph cell levels were significantly increased in the TR‐Ab (high) group compared to the TR‐Ab (low) group. Tph is localized in areas beyond lymphoid follicles and may extensively promote B‐cells in the inflamed thyroid gland. Conclusion This study demonstrates for the first time that Tph cells are significantly expanded in the blood and thyroid of GD patients. Similar to Tfh cells, Tph cells correlated with GD severity and B‐cell differentiation. Therefore, it may be a new target for GD immunotherapy.