Decrease in multiple complement proteins associated with development of islet autoimmunity and type 1 diabetes
Bobbie-Jo M. Webb-Robertson,
Ernesto S. Nakayasu,
Fran Dong,
Kathy C. Waugh,
Javier E. Flores,
Lisa M. Bramer,
Athena A. Schepmoes,
Yuqian Gao,
Thomas L. Fillmore,
Suna Onengut-Gumuscu,
Ashley Frazer-Abel,
Stephen S. Rich,
V. Michael Holers,
Thomas O. Metz,
Marian J. Rewers
Affiliations
Bobbie-Jo M. Webb-Robertson
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA; Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA; Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA; Corresponding author
Ernesto S. Nakayasu
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
Fran Dong
Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Kathy C. Waugh
Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Javier E. Flores
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
Lisa M. Bramer
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
Athena A. Schepmoes
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
Yuqian Gao
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
Thomas L. Fillmore
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
Suna Onengut-Gumuscu
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
Ashley Frazer-Abel
Divison of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Stephen S. Rich
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
V. Michael Holers
Divison of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Thomas O. Metz
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
Marian J. Rewers
Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Corresponding author
Summary: 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 disease onset. Our results suggest that children who exhibit islet autoimmunity and progress to clinical T1D have lower complement protein levels relative to those who do not progress within a similar time frame. 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.
