Identification of Autoantibodies to a Hybrid Insulin Peptide in Type 1 Diabetes

Author:

Wenzlau Janet M.1,Gu Yong2,Michels Aaron2ORCID,Rewers Marian2ORCID,Haskins Kathryn1,Yu Liping2ORCID

Affiliation:

1. Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 East 19th Avenue, Mail Stop 8333, Aurora, CO 80045, USA

2. Barbara Davis Center for Childhood Diabetes, 1775 Aurora Court, Mail Stop B140, Aurora, CO 80045, USA

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease that attacks the insulin-producing b cells of the pancreatic islets. Autoantibodies to b cell proteins typically appear in the circulation years before disease onset, and serve as the most accurate biomarkers of T1D risk. Our laboratory has recently discovered novel b cell proteins comprising hybrid proinsulin:islet amyloid polypeptide peptides (IAPP). T cells from a diabetic mouse model and T1D patients are activated by these hybrid peptides. In this study, we asked whether these hybrid molecules could serve as antigens for autoantibodies in T1D and prediabetic patients. We analyzed sera from T1D patients, prediabetics and healthy age-matched donors. Using a highly sensitive electrochemiluminescence assay, sera were screened for binding to recombinant proinsulin:IAPP probes or truncated derivatives. Our results show that sera from T1D patients contain antibodies that bind larger hybrid proinsulin:IAPP probes, but not proinsulin or insulin, at significantly increased frequencies compared to normal donors. Examination of sera from prediabetic patients confirms titers of antibodies to these hybrid probes in more than 80% of individuals, often before seroconversion. These results suggest that hybrid insulin peptides are common autoantigens in T1D and prediabetic patients, and that antibodies to these peptides may serve as valuable early biomarkers of the disease.

Funder

National Institute of Health

Publisher

MDPI AG

Subject

Clinical Biochemistry

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