Poster 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 (#155)

Katharine Irvine 1 , Megan Delmastro 2 , Tristan Barnes 1 , Bernett T 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 E Connolly 3 , John Piganelli 2 , Ranjeny Thomas 1
  1. The University of Queensland Diamantina Institute , Translational Research Institute, Woolloongabba, Qld, Australia
  2. Diabetes Institute, Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA
  3. Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis 138648, Singapore
  4. Mater Medical Research Institute, Translational Research Institute, Woolloongabba, Qld, 4102, Australia
  5. Dpt of Pediatric Endocrinology , Mater Children’s Hospital, South Brisbane, Qld, 4101, Australia
  6. School of Population Health , The University of Queensland, Princess Alexandra Hospital,, Woolloongabba, Qld 4102, Australia

The number and titre of islet autoantibodies (AB+) in FDR predict who are at risk of progressing to T1D. Additional biomarkers are needed to elucidate immune-pathogenesis, stratify risk, to identify screening tools and therapeutic targets in at risk subjects before and after the development of auto-antibodies. In a cross-sectional design, we quantified peripheral blood (PB) NF-kB DNA binding, pro-inflammatory cytokine and stress gene expression, and 133 serum analytes in AB-, single AB+ and multiple AB+ FDR, and healthy control children (HC). Feature selection was used to identify biomarkers that predicted AB- FDR status from HC children, and the presence of multiple AB among AB+ FDR. Markers of stress and inflammatory, including RELB DNA binding, TNF mRNA expression, and serum soluble LAG3 significantly predicted AB- FDR from HC. Multiple AB+ FDR were predicted on the basis of clinical features (BMI percentile, 2h OGTT glucose levels, HbA1c and insulin resistance), as well as serum levels of the gastro-intestinal hormone peptide YY, and the chemokines IL-20 and XCL1. By clustering biomarkers correlated with significantly predictive variables, FDR segregated into 2 phenotypic groups dominated by ACTH levels. In summary the data sets suggest that subjects at risk of T1D differ in their physiological response to stress, innate and adaptive immunity, insulin resistance, blood glucose and appetite regulation.