RhoA with Associated TRAb or FT3 in the Diagnosis and Prediction of Graves' Ophthalmopathy.

During Graves' disease (GD) treatment, Graves' ophthalmopathy (GO) is often ignored because only mild ocular symptoms are present in early GD. Therefore, we performed isobaric tags for relative and absolute quantification (iTRAQ) analysis and measured relevant endocrine hormones to identify predisposing factors of GO. Serum samples from 3 patients with mild GD and GO and 3 patients with GD but without GO were analyzed by iTRAQ. Based on their clinical data, 60 patients with GD were divided into the GO-free and GO groups. All patients were followed up for 7 months. Their eye conditions and changes in related biochemical indexes were recorded. The iTRAQ results showed that RhoA expression was upregulated and correlated significantly with the tight junction pathway and immunity. The changes in FT3 and RhoA from baseline to 7 months, the FT3 and RhoA baseline levels, and the TRAb titer levels in patients with GD significantly differed between the groups. ELISA and western blotting for RhoA, TRAb, and FT3 in the serum samples from GO patients showed significant upregulation, as well as elevated serum RhoA and TRAb levels in the mild stage of GO. At 7 months, the serum RhoA and FT3 levels were elevated. RhoA is a potential biomarker for mild GO. In GD patients, if an elevated serum RhoA level is accompanied by an elevated TRAb or FT3 level, GO is highly likely to occur, even when obvious ocular symptoms are absent.

Mutations in MC4R facilitate the angiogenic activity in patients with orbital venous malformation.

IMPACT STATEMENT: The detailed molecular mechanism of orbital venous malformation (OVM) is still not clear. Using whole exome sequencing, 4 types of melanocortin 4 receptor (MC4R) mutation were detected in 7 of 27 patients with OVM, and all types of MC4R mutations resulted in the upregulation of MC4R expression. In vitro study indicated that MC4R has impacts on the proliferation, cell cycle, migration, and tube formation of the endothelial cells. Moreover, MC4R mutations altered the downstream signaling, including cAMP concentration and the expression levels of several PI3K/AKT/mTOR downstream genes, including p21, cyclin B1, ITGA10, and ITGA11. MC4R mutations may lead to the pathogenesis of OVM through modulating the downstream signaling to alter the angiogenic activity of endothelial cells.