Shivani K Patel, Cindy S. Ma, K. Bell, R. Oram, W. Hagopian, S. Fourlanos, J. Greenfield
{"title":"免疫表型和遗传风险评分改善自身抗体阴性的1型糖尿病分类:研究方案","authors":"Shivani K Patel, Cindy S. Ma, K. Bell, R. Oram, W. Hagopian, S. Fourlanos, J. Greenfield","doi":"10.18203/2349-3259.ijct20222690","DOIUrl":null,"url":null,"abstract":"Background: An estimated 10-30% of type 1 diabetes (T1D) individuals do not have detectable autoantibodies at diagnosis, thus are classified as “idiopathic” or “non-immune.” Given the non-pathogenic role of islet autoantibodies, the validity of excluding an immune basis for disease in such individuals needs to be questioned. The pan-autoantibody negative type 1 diabetes in adults (PANDA) study aims to characterise the immune, clinical and metabolic phenotype of autoantibody negative T1D individuals.Methods: This is a two-part, multi-centre study which is recruiting 100 participants: autoantibody positive T1D (N=25), autoantibody negative T1D (N=25), latent autoimmune diabetes in adults (N=25) and age- and sex-matched normoglycaemic control (N=25) individuals. Study 1 involves baseline pathology collection and high dimensional immune-phenotyping using flow cytometry. DNA will be extracted from saliva samples to calculate type 1 diabetes genetic risk scores (T1DGRS). Autoantibody negative individuals will undergo monogenic diabetes testing. Study 2 is a prospective, longitudinal sub-study of study 1 participants within 5 years of diagnosis. Beta cell function will be assessed using glucagon stimulated C-peptide at 0, 9 and 18 months. The primary outcome of study 1 is to determine the phenotype of immune cells in autoantibody positive and negative T1D compared to healthy controls. Secondary outcomes of study 1 include clinical and metabolic characteristics and the T1DGRS. The primary outcome of study 2 is the rate of decline of stimulated C-peptide over time. Conclusions: The PANDA study is the first study of its kind which aims to improve diagnosis and characterisation of autoantibody negative T1D.","PeriodicalId":13787,"journal":{"name":"International Journal of Clinical Trials","volume":"55 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immunophenotype and genetic risk scores to improve autoantibody negative type 1 diabetes classification: study protocol\",\"authors\":\"Shivani K Patel, Cindy S. Ma, K. Bell, R. Oram, W. Hagopian, S. Fourlanos, J. Greenfield\",\"doi\":\"10.18203/2349-3259.ijct20222690\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: An estimated 10-30% of type 1 diabetes (T1D) individuals do not have detectable autoantibodies at diagnosis, thus are classified as “idiopathic” or “non-immune.” Given the non-pathogenic role of islet autoantibodies, the validity of excluding an immune basis for disease in such individuals needs to be questioned. The pan-autoantibody negative type 1 diabetes in adults (PANDA) study aims to characterise the immune, clinical and metabolic phenotype of autoantibody negative T1D individuals.Methods: This is a two-part, multi-centre study which is recruiting 100 participants: autoantibody positive T1D (N=25), autoantibody negative T1D (N=25), latent autoimmune diabetes in adults (N=25) and age- and sex-matched normoglycaemic control (N=25) individuals. Study 1 involves baseline pathology collection and high dimensional immune-phenotyping using flow cytometry. DNA will be extracted from saliva samples to calculate type 1 diabetes genetic risk scores (T1DGRS). Autoantibody negative individuals will undergo monogenic diabetes testing. Study 2 is a prospective, longitudinal sub-study of study 1 participants within 5 years of diagnosis. Beta cell function will be assessed using glucagon stimulated C-peptide at 0, 9 and 18 months. The primary outcome of study 1 is to determine the phenotype of immune cells in autoantibody positive and negative T1D compared to healthy controls. Secondary outcomes of study 1 include clinical and metabolic characteristics and the T1DGRS. The primary outcome of study 2 is the rate of decline of stimulated C-peptide over time. Conclusions: The PANDA study is the first study of its kind which aims to improve diagnosis and characterisation of autoantibody negative T1D.\",\"PeriodicalId\":13787,\"journal\":{\"name\":\"International Journal of Clinical Trials\",\"volume\":\"55 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-10-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Clinical Trials\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.18203/2349-3259.ijct20222690\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Clinical Trials","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.18203/2349-3259.ijct20222690","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Immunophenotype and genetic risk scores to improve autoantibody negative type 1 diabetes classification: study protocol
Background: An estimated 10-30% of type 1 diabetes (T1D) individuals do not have detectable autoantibodies at diagnosis, thus are classified as “idiopathic” or “non-immune.” Given the non-pathogenic role of islet autoantibodies, the validity of excluding an immune basis for disease in such individuals needs to be questioned. The pan-autoantibody negative type 1 diabetes in adults (PANDA) study aims to characterise the immune, clinical and metabolic phenotype of autoantibody negative T1D individuals.Methods: This is a two-part, multi-centre study which is recruiting 100 participants: autoantibody positive T1D (N=25), autoantibody negative T1D (N=25), latent autoimmune diabetes in adults (N=25) and age- and sex-matched normoglycaemic control (N=25) individuals. Study 1 involves baseline pathology collection and high dimensional immune-phenotyping using flow cytometry. DNA will be extracted from saliva samples to calculate type 1 diabetes genetic risk scores (T1DGRS). Autoantibody negative individuals will undergo monogenic diabetes testing. Study 2 is a prospective, longitudinal sub-study of study 1 participants within 5 years of diagnosis. Beta cell function will be assessed using glucagon stimulated C-peptide at 0, 9 and 18 months. The primary outcome of study 1 is to determine the phenotype of immune cells in autoantibody positive and negative T1D compared to healthy controls. Secondary outcomes of study 1 include clinical and metabolic characteristics and the T1DGRS. The primary outcome of study 2 is the rate of decline of stimulated C-peptide over time. Conclusions: The PANDA study is the first study of its kind which aims to improve diagnosis and characterisation of autoantibody negative T1D.