Uterus Globulin Associated Protein 1 (UGRP1) Is a Potential Marker of Progression of Graves' Disease into Hypothyroidism

Abstract

Background: Graves' disease (GD) and Hashimoto's thyroiditis (HT) were the two common types of autoimmune thyroid disease (AITD) characterized by hyperthyroidism and hypothyroidism, respectively. Approximately 20% of GD patients may result eventually in hypothyroidism in their natural course. Methods: Expression of Uterus globulin associated protein 1 (UGRP1) was assessed in the thyroid of AITD patients (293 HT and 198 GD) using IHC. The lymphocytes infiltration and serum TPOAb were analyzed. The co-expression of FAS and HLA-DR with UGRP1 was also measured in the thyroid of AITD patients by IHC. RT-qPCR was used to detect Th1/Th2 cytokines and IL-1β mRNA expression in the thyroid tissues. The mechanism of UGRP1 expression was evaluated in primary cultured thyrocytes treated with different cytokines. Findings: We found that UGRP1 was positive expressed in the thyrocytes of most HT patients and a proportion of GD patients. The pathologic features of UGRP1-positive thyrocytes resembled Hurthle cells, and were surrounded by infiltrated lymphocytes. The positivity rate of TPOAb in UGRP1-positive GD patients was much higher than that in -negative GD patients. Moreover, UGRP1 was co-expressed with Fas and HLA-DR in the thyrocytes of AITD patients. We also found IL-1β but not Th1 or Th2 cytokines was able to upregulate the expression of UGRP1 in AITD. Interpretation: Our findings indicated that UGRP1 may be as a novel marker in thyrocytes to predict GD patients who develop hypothyroidism. Funding: This work was supported by the National Natural Science Foundation of China (Grant No. 81770786 and 81500602). Declaration of Interest: The authors have declared that no conflict of interest exists. Ethical Approval: This study was approved by the Independent Ethics Committee of Shanghai Ninth People’s Hospital affiliated to Shanghai JiaoTong University School of Medicine (NO. 2017189). All written informed consents were received from participants prior to inclusion in the study.