Webb-Robertson BM, Nakayasu ES, Dong F, Waugh KC, Flores JE, Bramer LM, Schepmoes AA, Gao Y, Fillmore TL, Onengut-Gumuscu S, Frazer-Abel A, Rich SS, Holers VM, Metz TO, Rewers MJ. Decrease in multiple complement proteins associated with development of islet autoimmunity and type 1 diabetes. iScience. 2023 Dec 20;27(2):108769. doi: 10.1016/j.isci.2023.108769. PMID: 38303689; PMCID: PMC10831269.
Type 1 diabetes (T1D) is a chronic condition caused by autoimmune destruction of the insulin-producing pancreatic β-cells. While it is known that gene-environment interactions play a key role in triggering the autoimmune process leading to T1D, the pathogenic mechanism leading to the appearance of islet autoantibodies - biomarkers of autoimmunity – is poorly understood. Here we show that disruption of the complement system precedes the detection of islet autoantibodies and persists through diagnosis. Our results suggest that children who exhibit islet autoimmunity and progress to clinical T1D are complement deficient relative to those who do not progress within a similar timeframe. Thus, the complement pathway, an understudied mechanistic and therapeutic target in T1D, merits increased attention for use as protein biomarkers of prediction and potentially prevention of T1D.