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

doi:10.1016/j.isci.2023.108769

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. eCollection 2024 Feb 16.

Authors

Bobbie-Jo M Webb-Robertson^{1

2

3

4}, Ernesto S Nakayasu¹, Fran Dong⁵, Kathy C Waugh⁵, Javier E Flores¹, Lisa M Bramer¹, Athena A Schepmoes¹, Yuqian Gao¹, Thomas L Fillmore¹, Suna Onengut-Gumuscu⁶, Ashley Frazer-Abel⁷, Stephen S Rich⁶, V Michael Holers⁷, Thomas O Metz¹, Marian J Rewers⁵

Affiliations

¹ Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
² Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
³ Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
⁴ Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA.
⁵ Barbara Davis Center for Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁶ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁷ Divison of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Abstract

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.

Keywords: Diabetology; Immunology; Proteomics.

Abstract

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