Immunophenotype and genetic risk scores to improve autoantibody negative type 1 diabetes classification: study protocol


  • Shivani K. Patel Department of Diabetes and Metabolism, UNSW Sydney, Sydney, NSW, Australia St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia
  • Cindy S. Ma Human Immune Disorders, Garvan Institute of Medical Research, Sydney, NSW, Australia St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia
  • Kirstine J. Bell Charles Perkins Centre, Sydney Medical School, NSW, Australia The Children’s Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Australia
  • Richard Oram Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom
  • William A. Hagopian Pacific Northwest Research Institute, Seattle, Washington, USA
  • Spiros Fourlanos Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, VIC, Australia
  • Jerry R. Greenfield 1Department of Diabetes and Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia



Autoantibody-negative, Type 1 diabetes, Autoimmune diabetes, Immune phenotype, Characterisation


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.

Author Biography

Shivani K. Patel, Department of Diabetes and Metabolism, UNSW Sydney, Sydney, NSW, Australia St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia

PhD Candidate

Visiting Endocrinologist


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