Antibodies to post-translationally modified insulin in type 1 diabetes

Diabetologia
Rocky StrolloAhuva Nissim

Abstract

Insulin is the most specific beta cell antigen and a potential primary autoantigen in type 1 diabetes. Insulin autoantibodies (IAAs) are the earliest marker of beta cell autoimmunity; however, only slightly more than 50% of children and even fewer adults newly diagnosed with type 1 diabetes are IAA positive. The aim of this investigation was to determine if oxidative post-translational modification (oxPTM) of insulin by reactive oxidants associated with islet inflammation generates neoepitopes that stimulate an immune response in individuals with type 1 diabetes. oxPTM of insulin was generated using ribose and various reactive oxygen species. Modifications were analysed by SDS-PAGE, three-dimensional fluorescence and MS. Autoreactivity to oxPTM insulin (oxPTM-INS) was observed by ELISA and western blotting, using sera from participants with type 1 or type 2 diabetes and healthy controls as probes. IAA was measured using the gold-standard radiobinding assay (RBA). MS of oxPTM-INS identified chlorination of Tyr16 and Tyr26; oxidation of His5, Cys7 and Phe24; and glycation of Lys29 and Phe1 in chain B. Significantly higher binding to oxPTM-INS vs native insulin was observed in participants with type 1 diabetes, with 84% sensitivit...Continue Reading

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Citations

May 12, 2016·Current Diabetes Reports·Rene J McLaughlinBart O Roep
Oct 11, 2016·Current Opinion in Immunology·Bart O RoepArnaud Zaldumbide
Jul 15, 2016·Pediatric Diabetes·Mikael KnipRiitta Veijola
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Jul 17, 2020·Frontiers in Endocrinology·Marina PrimaveraFrancesco Chiarelli
Nov 8, 2018·Diabetologia·Stuart I ManneringColleen M Elso
Mar 22, 2021·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Mohd Talha Moinuddin
May 7, 2021·Frontiers in Immunology·Teresa Rodriguez-CalvoJessica L Dunne
Jun 3, 2021·Vaccines·Ramona Clemen, Sander Bekeschus

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