Project title
葛瑞夫茲氏病及抗甲狀腺藥物引起副作用之遺傳學研究與免疫學分析
Internal ID
MOST105-2314-B002-097-MY3
Principal Investigator
Start Date
August 1, 2018
End Date
July 31, 2019
Investigators
Organizations
Partner Organizations
Genetic Study and Immunological Analysis of Graves' Disease and Antithyroid Drug-Induced Adverse Effects = 葛瑞夫茲氏病及抗甲狀腺藥物引起副作用之遺傳學研究與免疫學分析
Description
This project is designed to work on various aspects of Graves5 disease (GD, MIM 27500), anti thyroid drug (ATD)-induced agranulocytosis (TiA) and ATD-induced cutaneous reaction (TiCR). GD is the leading cause of hyperthyroidism with both clinical and academic importance. The major treatment choice might cause significant adverse effects, which might be genetically determined and immune-mediated. TiA is the most feared adverse effect, which can be fatal if not detected and treated early. We are the leading team in the world working on TiA genetic study, and recently discovered that both class I (HLA-B*38:02) and class II (HLA-DRBHS^S) HLA genes were major genetic determinants of TiA. However, several unsolved mysteries remain at this moment, waiting for an ultimate study to provide the answers. TiCR is a common troublesome adverse effect hampering ATD treatment. To our knowledge, there was no previous published genetic study conducted for TiCR. Our pilot TiCR genetic study showed promising results and identify HLA-DQB1 *05:02 as the major susceptibility gene. A large-scale well-powered study will open the new field on TiCR. There has been no study on prospective cohort of GD patients for critical fundamental profiles. The Hematological and immunological profiles (including immune repertoire, iRepertoire) of GD, after ATD treatment and during TiA and/or TiCR development are largely unavailable. With the above-mentioned limitations in mind, we design this project with three major aims. Our Aim 1 is to conduct the ultimate genetic study of TiA, our Aim 2 is to perform the first well-powered genetic study of TiCR, and our Aim 3 is to profile hematological and immunological patterns for GD, TiA and TiCR in a prospective way. For Aim 1, although our sample size of TiA cohort is already world number one at this moment, we will more than double our sample size by recruiting additional 60 TiA patients, thanks to the valuable collaboration with Taipei Veterans General Hospital and Linkou Chang Gung Memorial Hospital. We hope to solve most of the remaining mysteries of TiA, and we believe that our results from Taiwan will be written to textbooks in the future. For Aim 2, our TiCR study will be the first well-powered genetic study of ATD-induced cutaneous reactions. We will identify TiCR patients from 1,000 existed GD patients and prospectively from 〜300 newly diagnosed GD patients. Very likely we will identify major genetic determinants of TiCR, and also open a new field for future studies. Our “Aim 3” will generate lots of critical and illuminating data/analyses. We will recruit 1,000 newly diagnosed GD patients in three years. The hematologcial and immunological profile after ATD treatment and during the development of TiA and TiCR can be recorded. We further can investigate the relationship between GD iRepertoire and various HLA genotypes. Lots of valuable biological samples will be preserved during this period for further study and analysis in the future. And for the first time in history we can explore the evolution of iRepertoire during GD course and during the development of TiA and TiCR.