Decrease in multiple complement proteins associated with development of islet autoimmunity and type 1 diabetes

Webb-Robertson, Bobbie-Jo M.; Nakayasu, Ernesto S.; Dong, Fran; Waugh, Kathy C.; Flores, Javier E.; Bramer, Lisa M.; Schepmoes, Athena A.; Gao, Yuqian; Fillmore, Thomas L.; Onengut-Gumuscu, Suna; Frazer-Abel, Ashley; Rich, Stephen S.; Holers, V. Michael; Metz, Thomas O.; Rewers, Marian J.

doi:10.1016/j.isci.2023.108769

Decrease in multiple complement proteins associated with development of islet autoimmunity and type 1 diabetes

Journal Article · Wed Dec 20 00:00:00 EST 2023 · iScience

DOI:https://doi.org/10.1016/j.isci.2023.108769· OSTI ID:2375811

Webb-Robertson, Bobbie-Jo M. ^[1]; Nakayasu, Ernesto S. ^[2]; Dong, Fran ^[3]; Waugh, Kathy C. ^[3]; Flores, Javier E. ^[2]; Bramer, Lisa M. ^[2]; Schepmoes, Athena A. ^[2]; Gao, Yuqian ^[2]; Fillmore, Thomas L. ^[2]; Onengut-Gumuscu, Suna ^[4]; Frazer-Abel, Ashley ^[3]; Rich, Stephen S. ^[4]; Holers, V. Michael ^[3]; Metz, Thomas O. ^[2]; Rewers, Marian J. ^[3]

Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Univ. of Colorado Anschutz Medical Campus, Aurora, CO (United States); Univ. of Florida, Gainesville, FL (United States); Oregon Health & Science Univ., Portland, OR (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Univ. of Colorado Anschutz Medical Campus, Aurora, CO (United States)
Univ. of Virginia, Charlottesville, VA (United States)

Type 1 diabetes (T1D) is a chronic condition caused by autoimmune destruction of the insulin-producing pancreatic ß-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.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: Helmsley Charitable Trust; National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2375811

Report Number(s):: PNNL-SA--177389

Journal Information:: iScience, Journal Name: iScience Journal Issue: 2 Vol. 27; ISSN 2589-0042

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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