Oral Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Analysis of immune, metabolic and clinical biomarkers implicates inflammatory and stress pathways in the pre-clinical development of type 1 diabetes (#44)

Ranjeny Thomas 1 , Katharine Irvine 1 , Megan Delmastro 2 , Tristan Barnes 1 , Bernett Lee 3 , Ming-Fen Ho 1 , Mamdouh Sedhom 1 , Danielle Borg 4 , Au Bijin 3 , Josephine Forbes 4 , Andrew Cotterill 5 , Mark Harris 5 , Sanjoy Paul 6 , John Connolly 3 , Jon Piganelli 2
  1. Translational Research Institute, The University of Queensland Diamantina Institute, Brisbane
  2. Diabetes Institute, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
  3. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore
  4. Mater Medical Research Institute, , Translational Research Institute, Brisbane
  5. Department of Pediatric Endocrinology, , Mater Children’s Hospital, Brisbane
  6. School of Population Health, The University of Queensland, Brisbane
In type 1 diabetes (T1D), autoimmune-mediated destruction of pancreatic b-cells results in diabetes. Although islet autoantibodies (AB) identify individuals progressing to T1D, additional biomarkers are needed to elucidate disease immunopathogenesis. In a cross-sectional design, we quantified peripheral blood (PB) NF-kB DNA binding, pro-inflammatory cytokine and stress gene expression, and serum analytes in AB+ and AB- first degree relative (FDR) and healthy control children. Using feature selection, stress and inflammatory biomarkers, including RELB DNA binding and serum soluble LAG3 significantly predicted AB- FDR from healthy controls. Clinical, inflammatory and gastro-intestinal hormone biomarkers, including IL-20 and peptide YY significantly predicted FDR with multiple AB. By clustering biomarkers correlated with significantly predictive variables, FDR segregated into 2 phenotypic groups dominated by serum ACTH. These biomarker sets suggest that groups of subjects at risk of T1D differ in their physiological response to stress, innate and adaptive immunity, insulin resistance, blood glucose and appetite regulation.