Plasma protein biomarkers predict the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity - Centre for Population Health Research (POPC) - A joint centre by the University of Turku and the municipal authority of the Hospital District of Southwest Finland. The goal of Centre for Population Health Research is to promote health and well-being of society by enhancing research and development work on clinical-epidemiological population research.

Cell Rep Med. 2023 Jun 23:101093. doi: 10.1016/j.xcrm.2023.101093. Online ahead of print.

ABSTRACT

Type 1 diabetes (T1D) results from autoimmune destruction of β cells. Insufficient availability of biomarkers represents a significant gap in understanding the disease cause and progression. We conduct blinded, two-phase case-control plasma proteomics on the TEDDY study to identify biomarkers predictive of T1D development. Untargeted proteomics of 2,252 samples from 184 individuals identify 376 regulated proteins, showing alteration of complement, inflammatory signaling, and metabolic proteins even prior to autoimmunity onset. Extracellular matrix and antigen presentation proteins are differentially regulated in individuals who progress to T1D vs. those that remain in autoimmunity. Targeted proteomics measurements of 167 proteins in 6,426 samples from 990 individuals validate 83 biomarkers. A machine learning analysis predicts if individuals would remain in autoimmunity or develop T1D 6 months before autoantibody appearance, with areas under receiver operating characteristic curves of 0.871 and 0.918, respectively. Our study identifies and validates biomarkers, highlighting pathways affected during T1D development.

PMID:37390828 | DOI:10.1016/j.xcrm.2023.101093