TALENT EDUCATION

Researchers from Xi’an Jiaotong University confirmed that rapamycin is an important breakthrough in the treatment of the cause of Graves’ eye disease


Graves’ ophthalmopathy (GO) is an autoimmune response-mediated orbital inflammatory disease characterized by proptosis, pain, and impaired vision. The decline in quality of life in patients with GO is severe, even lower than in patients with diabetes, COPD and heart failure. The current treatment of GO is mainly for patients with moderate to severe activity, glucocorticoids are given to extensively suppress immune and inflammatory responses, and patients with insignificant drug treatment effect or rapid deterioration of vision require surgery. In recent years, the academic community has continuously explored the pathogenesis of GO and carried out targeted therapies for different links, such as mycophenolate mofetil and IGF-1R monoclonal antibody, which have achieved certain results. Therefore, exploring the pathogenesis of GO and finding specific therapeutic targets has always been a hot spot and difficulty at the forefront of the field.
In response to the above problems, the team of Professor Shi Bingyin and Dr. Wang Yue, Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi’an Jiaotong University, with the support of a number of National Natural Science Foundation of China, has carried out basic to clinical research on the pathogenesis and therapeutic targets of GO (from bench to bedside) in the past ten years. The team has previously discovered through single-cell RNA sequencing that there is a group of CD4+ toxic T cells (CTLs) characterized by inflammation and chemotaxis in the peripheral blood of GO patients, which is a possible new target for GO treatment. For this target, the team chose the immunosuppressant rapamycin as a potential treatment option. Through animal models, in vitro experiments and clinical interventions, the research team confirmed that rapamycin can not only reduce the incidence of GO mice from 87.5% to 37.5% by targeting CD4+ CTL cells, but also effectively improve the diplopia symptoms and clinical activity scores of hormone-tolerant GO patients. Therefore, rapamycin is a promising potential drug for the treatment of GO.

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The results were recently published in The Journal of Clinical under the title “Rapamycin improves Graves’ orbitopathy by suppressing CD4+ cytotoxic T lymphocytes.” Investigation(JCI)Insight。 Dr. Meng Zhang of the First Affiliated Hospital of Xi’an Jiaotong University, Professor Kelvin K. L. Chong of the University of Hong Kong Chinese, Dr. Ziyi Chen of the First Affiliated Institute of Xi’an Jiaotong University are the co-first authors of the paper, Professor George J. Kahaly of Johannes Gutenberg University in Germany, Professor Shi Bingyin and Dr. Wang Yue of the First Affiliated Hospital of Xi’an Jiaotong University are the co-corresponding authors of the paper. This is following the group’s development of a predictive model of GO in the Graves hyperthyroid cohort (Clinical and translational medicine) through T cell receptor (TCR) sequencing, and single-cell RNA sequencing found and identified a group of GO-specific CD4+ CTL cells (Cellular & molecular immunology). After the establishment and systematic evaluation of a mouse model of GO (Thyroid), another new development in the basic-clinical field of GO.
Based on this new progress in GO treatment, the team of Professor Shi Bingyin and Dr. Wang Yue has carried out a national multi-center clinical study of rapamycin in the treatment of GO. The study was led by the First Affiliated Hospital of Xi’an Jiaotong University, including Beijing Tongren Hospital affiliated to Capital Medical University, Shunde Hospital of Southern Medical University, and Tangdu Hospital of Air Force Military Medical University.
Paper Link:https://insight.jci.org/articles/view/160377

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Shi Bingyin, Chief Physician, Doctoral Supervisor, Second-level Professor. Vice President of the 4th Committee of the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, Vice President of the Shaanxi Medical Doctor Association, President of the Endocrinology and Metabolism Branch of the Shaanxi Medical Doctor Association, member of the expert group of the Central Health Bureau, expert of the State Council Special Allowance, and young and middle-aged expert with outstanding contributions to the Health Commission. He has won the Wu Jieping Medical Research Award, the Chinese Physician Award, the National May Day Labor Medal and the title of “National Medical Ethics Pacesetter”. He has been committed to the basic and clinical research of thyroid and diabetes for a long time, and is the first in the world to propose a new theory of prevention of hyperthyroidism by inducing immune tolerance, and is independently developing a vaccine to prevent hyperthyroidism. In recent years, with the support of the key research and development plan of the Ministry of Science and Technology, systematic research has been carried out in the fields of diabetes and other major chronic diseases management and the whole life cycle health management of the whole population, and a number of major research results have been achieved.

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Yue Wang, associate researcher, attending physician, postdoctoral fellow in control science and engineering, young science and technology rising star in Shaanxi Province. Member of the Thyroid Group of the Endocrinology Branch of the Chinese Medical Association, Member of the Endocrinology and Metabolism Physician Branch of Shaanxi Medical Association, Member of the American Endocrine Society, Secretary of the Northwest Pituitary Tumor Alliance, Deputy Director of the Science and Technology Department of the First Affiliated Hospital of Xi’an Jiaotong University (temporary position). His research interests include the pathogenesis of autoimmune thyroid diseases and immune prevention and treatment, chronic disease prevention, etc., and in the past three years, he has published 9 SCI papers as the first or corresponding author, with a cumulative impact factor of 80 points. He presided over 2 National Natural Science Foundation of China, participated in 2 key R&D plans of the Ministry of Science and Technology as a research backbone, and was approved 4 national invention patents.

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Meng Zhang, assistant researcher, resident physician, member of the “Excellent Medical Youth Training Program” of the First Affiliated Hospital of Xi’an Jiaotong University. His research direction is the pathogenesis of autoimmune thyroid disease and immune prevention, and he has published 10 articles, including 8 SCI, participated in the compilation of 2 monographs, and 1 invention patent. He has presided over 1 project of the National Natural Science Foundation of China, participated in 3 projects of the National Natural Science Foundation of China, and 1 provincial scientific research plan.
 
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