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

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

Journal Article · 19 December 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)

Cite

Export

Save

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

References (40)

Seroconversion to Multiple Islet Autoantibodies and Risk of Progression to Diabetes in Children Ziegler, Anette G.; Rewers, Marian; Simell, Olli JAMA, Vol. 309, Issue 23 https://doi.org/10.1001/jama.2013.6285	journal	June 2013
Tumour extracellular vesicle‐derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement‐dependent cytotoxicity of tumour cells Mao, Xiaowen; Zhou, Longyin; Tey, Sze Keong Journal of Extracellular Vesicles, Vol. 10, Issue 1 https://doi.org/10.1002/jev2.12031	journal	November 2020
The complement system in Type 1 (insulin-dependent) diabetes Charlesworth, J. A.; Timmermans, V.; Golding, J. Diabetologia, Vol. 30, Issue 6 https://doi.org/10.1007/BF00292537	journal	June 1987
C3aR and C5aR1 act as key regulators of human and mouse β-cell function Atanes, Patricio; Ruz-Maldonado, Inmaculada; Pingitore, Attilio Cellular and Molecular Life Sciences, Vol. 75, Issue 4 https://doi.org/10.1007/s00018-017-2655-1	journal	September 2017
The complement system in age-related macular degeneration Armento, Angela; Ueffing, Marius; Clark, Simon J. Cellular and Molecular Life Sciences, Vol. 78, Issue 10 https://doi.org/10.1007/s00018-021-03796-9	journal	March 2021
Peptide serum markers in islet autoantibody-positive children von Toerne, Christine; Laimighofer, Michael; Achenbach, Peter Diabetologia, Vol. 60, Issue 2 https://doi.org/10.1007/s00125-016-4150-x	journal	November 2016
Late-onset islet autoimmunity in childhood: the Diabetes Autoimmunity Study in the Young (DAISY) Frohnert, Brigitte I.; Ide, Lisa; Dong, Fran Diabetologia, Vol. 60, Issue 6 https://doi.org/10.1007/s00125-017-4256-9	journal	March 2017
Integrated glycomics and genetics analyses reveal a potential role for N-glycosylation of plasma proteins and IgGs, as well as the complement system, in the development of type 1 diabetes Rudman, Najda; Kaur, Simranjeet; Simunović, Vesna Diabetologia, Vol. 66, Issue 6 https://doi.org/10.1007/s00125-023-05881-z	journal	March 2023
Newborn screening for HLA markers associated with IDDM: Diabetes Autoimmunity Study in the Young (DAISY) Rewers, M.; Bugawan, T. L.; Norris, J. M. Diabetologia, Vol. 39, Issue 7 https://doi.org/10.1007/s001250050514	journal	July 1996
Feasibility of genetic and immunological prediction of Type I diabetes in a population-based birth cohort Kupila, A.; Muona, P.; Simell, T. Diabetologia, Vol. 44, Issue 3 https://doi.org/10.1007/s001250051616	journal	March 2001
A Systematic Investigation of Complement and Coagulation-Related Protein in Autism Spectrum Disorder Using Multiple Reaction Monitoring Technology Cao, Xueshan; Tang, Xiaoxiao; Feng, Chengyun Neuroscience Bulletin, Vol. 39, Issue 11 https://doi.org/10.1007/s12264-023-01055-4	journal	April 2023
Complement Component C3 Is Highly Expressed in Human Pancreatic Islets and Prevents β Cell Death via ATG16L1 Interaction and Autophagy Regulation King, Ben C.; Kulak, Klaudia; Krus, Ulrika Cell Metabolism, Vol. 29, Issue 1 https://doi.org/10.1016/j.cmet.2018.09.009	journal	January 2019
Complement analysis 2016: Clinical indications, laboratory diagnostics and quality control Prohászka, Zoltán; Nilsson, Bo; Frazer-Abel, Ashley Immunobiology, Vol. 221, Issue 11 https://doi.org/10.1016/j.imbio.2016.06.008	journal	November 2016
Temporal profiles of plasma proteome during childhood development Liu, Chih-Wei; Bramer, Lisa; Webb-Robertson, Bobbie-Jo Journal of Proteomics, Vol. 152 https://doi.org/10.1016/j.jprot.2016.11.016	journal	January 2017
Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression Liu, Chih-Wei; Bramer, Lisa; Webb-Robertson, Bobbie-Jo Journal of Proteomics, Vol. 172 https://doi.org/10.1016/j.jprot.2017.10.004	journal	February 2018
Role of complement in diabetes Ajjan, Ramzi A.; Schroeder, Verena Molecular Immunology, Vol. 114 https://doi.org/10.1016/j.molimm.2019.07.031	journal	October 2019
Plasma protein biomarkers predict the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity Nakayasu, Ernesto S.; Bramer, Lisa M.; Ansong, Charles Cell Reports Medicine, Vol. 4, Issue 7 https://doi.org/10.1016/j.xcrm.2023.101093	journal	July 2023
Rapidly Assessing the Quality of Targeted Proteomics Experiments through Monitoring Stable-Isotope Labeled Standards Gibbons, Bryson C.; Fillmore, Thomas L.; Gao, Yuqian Journal of Proteome Research, Vol. 18, Issue 2 https://doi.org/10.1021/acs.jproteome.8b00688	journal	December 2018
Tutorial: best practices and considerations for mass-spectrometry-based protein biomarker discovery and validation Nakayasu, Ernesto S.; Gritsenko, Marina; Piehowski, Paul D. Nature Protocols, Vol. 16, Issue 8 https://doi.org/10.1038/s41596-021-00566-6	journal	July 2021
Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study Törn, Carina; Liu, Xiang; Hagopian, William Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep27887	journal	June 2016
Complement Walport, Mark J. New England Journal of Medicine, Vol. 344, Issue 14 https://doi.org/10.1056/NEJM200104053441406	journal	April 2001
The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes Wenzlau, J. M.; Juhl, K.; Yu, L. Proceedings of the National Academy of Sciences, Vol. 104, Issue 43, p. 17040-17045 https://doi.org/10.1073/pnas.0705894104	journal	October 2007
Peeking Inside the Black Box: Visualizing Statistical Learning With Plots of Individual Conditional Expectation Goldstein, Alex; Kapelner, Adam; Bleich, Justin Journal of Computational and Graphical Statistics, Vol. 24, Issue 1 https://doi.org/10.1080/10618600.2014.907095	journal	January 2015
Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes Zhang, Qibin; Fillmore, Thomas L.; Schepmoes, Athena A. The Journal of Experimental Medicine, Vol. 210, Issue 1 https://doi.org/10.1084/jem.20111843	journal	December 2012
Epidemiology of hypocomplementaemic urticarial vasculitis (anti-C1q vasculitis) Sjöwall, Christopher; Mandl, Thomas; Skattum, Lillemor Rheumatology, Vol. 57, Issue 8 https://doi.org/10.1093/rheumatology/key110	journal	April 2018
Prediction of the development of islet autoantibodies through integration of environmental, genetic, and metabolic markers Webb‐Robertson, Bobbie‐Jo M.; Bramer, Lisa M.; Stanfill, Bryan A. Journal of Diabetes, Vol. 13, Issue 2 https://doi.org/10.1111/1753-0407.13093	journal	August 2020
Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response Sarkar, Soumyadeep; Elliott, Emily C.; Henry, Hayden R. Clinical Proteomics, Vol. 20, Issue 1 https://doi.org/10.1186/s12014-023-09429-6	journal	September 2023
Integration of Infant Metabolite, Genetic, and Islet Autoimmunity Signatures to Predict Type 1 Diabetes by Age 6 Years Webb-Robertson, Bobbie-Jo M.; Nakayasu, Ernesto S.; Frohnert, Brigitte I. The Journal of Clinical Endocrinology & Metabolism, Vol. 107, Issue 8 https://doi.org/10.1210/clinem/dgac225	journal	April 2022
Protective Role of Complement C3 Against Cytokine-Mediated β-Cell Apoptosis Dos Santos, Reinaldo S.; Marroqui, Laura; Grieco, Fabio A. Endocrinology, Vol. 158, Issue 8 https://doi.org/10.1210/en.2017-00104	journal	June 2017
Low HERV-K(C4) Copy Number Is Associated With Type 1 Diabetes Mason, Mike J.; Speake, Cate; Gersuk, Vivian H. Diabetes, Vol. 63, Issue 5 https://doi.org/10.2337/db13-1382	journal	April 2014
Serum Proteomes Distinguish Children Developing Type 1 Diabetes in a Cohort With HLA-Conferred Susceptibility Moulder, Robert; Bhosale, Santosh D.; Erkkilä, Timo Diabetes, Vol. 64, Issue 6 https://doi.org/10.2337/db14-0983	journal	January 2015
Predictive Modeling of Type 1 Diabetes Stages Using Disparate Data Sources Frohnert, Brigitte I.; Webb-Robertson, Bobbie-Jo; Bramer, Lisa M. Diabetes, Vol. 69, Issue 2 https://doi.org/10.2337/db18-1263	journal	November 2019
Increased Complement Activation in Human Type 1 Diabetes Pancreata Rowe, Patrick; Wasserfall, Clive; Croker, Byron Diabetes Care, Vol. 36, Issue 11 https://doi.org/10.2337/dc13-0203	journal	October 2013
Distinct Growth Phases in Early Life Associated With the Risk of Type 1 Diabetes: The TEDDY Study Liu, Xiang; Vehik, Kendra; Huang, Yangxin Diabetes Care, Vol. 43, Issue 3 https://doi.org/10.2337/dc19-1670	journal	January 2020
2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2022 Diabetes Care, Vol. 45, Issue Supplement_1 https://doi.org/10.2337/dc22-S002	journal	December 2021
ICA512 Autoantibody Radioassay Gianani, Roberto; Rabin, Daniel U.; Verge, Charles F. Diabetes, Vol. 44, Issue 11 https://doi.org/10.2337/diab.44.11.1340	journal	November 1995
Perinatal Autoimmunity in Offspring of Diabetic Parents: The German Multicenter BABY-DIAB Study: Detection of Humoral Immune Responses to Islet Antigens in Early Childhood Roll, Ursula; Füchtenbusch, Martin; Ziegler, Anette-G Diabetes, Vol. 45, Issue 7 https://doi.org/10.2337/diab.45.7.967	journal	July 1996
Complement Activation in Inflammatory Skin Diseases Giang, Jenny; Seelen, Marc A. J.; van Doorn, Martijn B. A. Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.00639	journal	April 2018
Anaphylatoxins spark the flame in early autoimmunity Schanzenbacher, Jovan; Köhl, Jörg; Karsten, Christian M. Frontiers in Immunology, Vol. 13 https://doi.org/10.3389/fimmu.2022.958392	journal	July 2022
Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease Tang, Anqi; Zhao, Xin; Tao, Tian Frontiers in Immunology, Vol. 14 https://doi.org/10.3389/fimmu.2023.1229806	journal	September 2023

Similar Records

Serum biomarkers for diagnosis and prediction of type 1 diabetes

Journal Article · 2018 · Translational Research · OSTI ID:1503616

Yi, Lian; Swensen, Adam C.; Qian, Wei-Jun

Novel genetic risk factors influence progression of islet autoimmunity to type 1 diabetes

Journal Article · 2020 · Scientific Reports · OSTI ID:1713200

Onengut-Gumuscu, Suna; Paila, Umadevi; Chen, Wei-Min; +10 more

Serum biomarkers for diagnosis and prediction of type 1 diabetes

Journal Article · 2018 · Translational Research · OSTI ID:1464493

Yi, Lian; Swensen, Adam C.; Qian, Wei -Jun

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

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

Citation Formats

References (40)

Similar Records

Related Subjects