On November 5, the team led by Professor Shi Bingyin from the First Affiliated Hospital of Xi 'an Jiaotong University (XJTU) published an article online entitled "Predicting the early risk of ophthalmopathy in Graves’ disease patients using TCR repertoire" in the internationally renowned journal Clinical and Transitional Medicine, illustrating relevant research outcomes in the field of thyroid disease. This is another critical original finding achieved by this project after obtaining the software copyright certificate of Software for Immune Repertoire Statistics Construction in 2018 and the national invention patent of T-cell Data Processing Method and Device in 2020.
In this study, the research team has confirmed for the first time globally that use of T-cell antigen receptor (TCR) signatures in the peripheral blood of patients with initial onset of hyperthyroidism can predict the progression from hyperthyroidism into Graves’ ophthalmopathy. The researchers innovatively proposed an index to characterize the TCR signatures and successfully predict the progression of hyperthyroidism into Graves’ ophthalmopathy by using bioinformatics methods, making revolutionary advancements in the early diagnosis of Graves’ ophthalmopathy.
This study was jointly completed by two teams led by Professor Shi Bingyin from Department of Endocrinology of our hospital and Professor Ye Kai from Department of Telecommunications of XJTU. Our hospital is the first affiliation. Wang Yue from Department of Endocrinology of our hospital is the first author and Liu Yufeng from Biobank of our hospital is the co-first author. Professor Shi Bingyin is the corresponding author and Professor Ye Kai is the co-corresponding author.
The achievements made by two teams led by Professor Shi Bingyin and Professor Ye Kai in the same project are the perfect combination of clinical medicine and computational science, fully demonstrating the advantages of the scientific research modes of "combination of medicine and engineering" and "multidisciplinary cooperation".
In this study, the researchers demonstrated that the TCR information in the thyroid tissue is retained in the peripheral blood samples of patients with hyperthyroidism by sequencing the TCR repertoire of 135 patients and comprehensive bioinformatics analysis, indicating that the TCR information in the peri-ocular lesions of Graves’ ophthalmopathy patients will also be expressed in peripheral blood samples.
Although there is evidence supporting the distribution of TCR in the lesions in peripheral blood samples, it remains a huge challenge to identify the TCR that can characterize the progression of Graves’ ophthalmopathy from a large quantity of peripheral blood data. After countless analytical simulations and regression evaluations, the researchers eventually focused upon the clonal expansion of the TCR VJ family and the homology and similarity of its amino acid sequences. Under persistent antigen stimulation, the TCR capable of responding to antigens will experience changes of increased frequency and elevated sequence homology, which become more prominent within the VJ family. The researchers reproduced this phenomenon through a large quantity of data simulation. On this basis, they identified the VJ family dataset that could characterize the course of Graves’ ophthalmopathy from the TCR data of hyperthyroidism and Graves’ ophthalmopathy populations. Subsequently, they successfully constructed the prediction model for disease progression through classical statistical methods.
Duringsubsequent 1-year follow-up, 17 patients were predicted to be positive for Graves’ ophthalmopathy, and 12 of them presented with eyelid swelling and exophthalmos during the follow-up, who were diagnosed with Graves’ ophthalmopathy after periocular CT scan. The onset of Graves’ ophthalmopathy was observed from 4 to 10 months after initial onset of hyperthyroidism, 6.5 months on average. These findings indicate that TCR detection technique can make the diagnosis of Graves’ ophthalmopathy 6.5 months earlier compared with current clinical imaging-based tools, which plays a significant role in the early intervention and enhancing clinical prognosis of patients with Graves’ ophthalmopathy.