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Inna Starskaia from Riitta Lahesmaa lab succesfully defended her PhD thesis “Early immune response in children developing type 1 diabetes” on Friday the 15th of May. Her opponent was Professor Katri Lindfors from Tampere University.

Summary of the Dissertation:

Type 1 diabetes is a multifactorial autoimmune disorder. The pathogenesis of the disease is determined by the interplay of genetic and environmental factors, resulting in an aberrant immune response that leads to the destruction of insulin-secreting pancreatic beta cells. The appearance of islet-targeting autoantibodies, so called seroconversion, is currently the earliest biomarker for predicting the progression of type 1 diabetes before the clinical onset. One of the aims of this dissertation was to study early changes in immune responses that precede seroconversion in children who later progress to overt type 1 diabetes. In the first study we discovered numerous cell type-specific differential DNA methylation changes in circulating immune cells from children who later progressed to beta cell autoimmunity at the early stage of disease development, even prior to seroconversion. Another critical question addressed in this dissertation was the heterogeneity observed in the rate of disease progression to clinical disease as well as the post-onset beta cell decline. Recent studies reported on the existence of different disease pathways, or endotypes of type 1 diabetes behind one clinical phenotype. The second study revealed that the immune cell composition of peripheral blood mononuclear cells varied among children who later developed type 1 diabetes, when we compared children who had IAA, GADA or two autoantibodies detected as their first-appearing antibodies, supporting heterogeneity in the pathogenesis of the disease. Finally, in the third study we found that gene expression changes during the first year after clinical type 1 diabetes onset can predict the rate of disease progression. The predictive model allowed us to divide patients into rapid and slow progressors and was validated in an independent dataset of newly diagnosed type 1 diabetes patients. In conclusion, this dissertation presents findings on immune changes at the very early stage of type 1 diabetes development and support previous observations on heterogeneity of the disease.

Download the dissertation at UTUPub: https://urn.fi/URN:ISBN:978-952-02-0117-3