SAT-556 A New Marker for Distinguishing Hashimoto's Hyperthyroidism Subtype of GD Patients

Abstract

Uterus globulin associated protein 1 (UGRP1) encoded by scgb3a2,is a kind of uterus globulin/Clara cell secretory protein (UG/CCSP). UGRP1 is highly expressed in the epithelial cells of the trachea, bronchial, bronchial tubes, but weakly expressed in the thyroid gland. Positional cloning of candidate gene identified that scgb3a2 was a susceptibility gene for Graves’ disease (GD) in the Chinese Han population, which was further confirmed in the UK and Polish populations. However, the roles of UGRP1 in AITD is unknown. To illuminate the roles of UGRP1 in the pathogenesis of AITD, we detected the expression of UGRP1 in thyroid tissues from 491 AITD patients (including 198 cases of HT and 293 cases of GD), 109 cases of non-AITD patients and 18 cases of normal controls by immunohistochemical staining analysis. In result, UGRP1 was found highly expressed in thyroid tissues from most HT patients and partial GD patients, but barely expressed in thyroid from non-AITD patients and normal controls. The positive rates of UGRP1 in HT and GD patients were 88.4% and 24.7%, respectively. Besides, UGRP1 was found co-expressed with Fas and HLA-DR in the thyrocytes from patients with either HT or GD. By sorting the thyrocytes from patients with HT based on the Fas expression, we found that Fas-positive thyrocytes showed a higher UGRP1 mRNA levels than that in Fas-negative thyrocytes. Moreover, the numbers of infiltrated lymphocytes in the periphery of the thyrocytes was much more in UGRP1-positive thyrocytes than that in UGRP1-negative thyrocytes, indicating a positive correlation of UGRP1 and the autoimmune response in AITD. Clinical data also showed that the positive rate of the serum TPO antibody in the GD patients with UGRP1-positive was higher than that with UGRP1-negative. Furthermore, we investigated the association of inflammatory cytokines and UGRP1 and found the mRNA expression of IL-1β in thyroid from HT patients was much higher than that from GD patients, which was also higher in the thyroid from GD patients with UGRP1-positive than that with UGRP1-negative. And IL-1β induced UGRP1 expressions in both mRNA and protein levels in primary thyroid cells, probably explaining the expression of UGRP1 in thyrocytes. Consequently, we found for the first time that UGRP1 was highly expressed in thyroid from most HT patients and partial GD patients, positively associated with the infiltrated lymphocytes in the thyroid. The clinical and pathological characteristics of GD patients with UGRP1-positive in thyroid was similar to that of HT patients. Therefore, we identified that UGRP1 may be a marker of the “hashimoto’s hyperthyroidism” subtype of GD patients.