Abnormal Elevation of the Expression of Costimulatory Molecule CD226 in Graves' Disease: Two Cross-Sectional Studies.

Abstract

Objective: This study aimed to explore the differential expression of the co-stimulatory molecule CD226 in lymphocytes from patients with New-Onset Graves' Disease (NOGD) and its correlation with clinical indicators.

Methods: Sixty-eight participants were recruited for the discovery experiment (NOGD: healthy control (HC) = 39:29). Peripheral Blood Mononuclear Cells (PBMCs) were isolated. Flow cytometry was performed to detect CD226 expression on multiple lymphocyte subtypes. CD226 mRNA expression in PBMCs was detected by qPCR. Fifty-eight participants were recruited for the validation experiment (NOGD: HC=35:23). CD4+ T cells were isolated, and the level of CD226 mRNA in CD4+ T cells was detected. Five cases of each of Graves' disease (GD) thyroid and control thyroid were collected for CD226 immunohistochemical staining.

Results: CD226 expression was the highest in monocytes (NOGD: 94.1% vs. HC: 94.8%) and the lowest in CD8+ T cells (NOGD: 65.3% vs. HC: 64.9%). Compared with HC, CD226 expression on the CD4+ T cells increased in the peripheral blood of NOGD patients and correlated with TPO-Ab. Meanwhile, CD226 mRNA levels were elevated in CD4+ T cells and positively correlated with TR-Ab. CD226 expression was significantly increased in the thyroid tissues of GD patients.

Conclusion: This study demonstrates for the first time the elevated expression of CD226 in CD4+ T cells and thyroid tissue of NOGD. The abnormal elevation of CD226 is correlated with clinical indicators. It suggests that the co-stimulatory molecule CD226 is involved in the pathogenesis of GD.