Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children

Diabetologia
Rocky StrolloAhuva Nissim

Abstract

We have shown that autoimmunity to insulin in type 1 diabetes may result from neoepitopes induced by oxidative post-translational modifications (oxPTM). Antibodies specific to oxPTM-insulin (oxPTM-INS-Ab) are present in most newly diagnosed individuals with type 1 diabetes and are more common than autoantibodies to native insulin. In this study, we investigated whether oxPTM-INS-Ab are present before clinical onset of type 1 diabetes, and evaluated the ability of oxPTM-INS-Ab to identify children progressing to type 1 diabetes. We used serum samples collected longitudinally from the 'All Babies in Southeast Sweden (ABIS)' cohort tested for the gold standard islet autoantibodies to insulin (IAA), GAD (GADA), tyrosine phosphatase 2 (IA-2A) and zinc transporter 8 (ZnT8A). We studied 23 children who progressed to type 1 diabetes (progr-T1D) and 63 children who did not progress to type 1 diabetes (NP) after a median follow-up of 10.8 years (interquartile range 7.7-12.8). Of the latter group, 32 were positive for one or more islet autoantibodies (NP-AAB+). oxPTM-INS-Ab to insulin modified by •OH or HOCl were measured by our developed ELISA platform. Antibodies to at least one oxPTM-INS were present in 91.3% of progr-T1D children. oxP...Continue Reading

References

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Citations

Dec 2, 2017·Pediatric Diabetes·Dorothy Becker, Richard Insel
Nov 8, 2018·Diabetologia·Stuart I ManneringColleen M Elso
Jun 4, 2019·Critical Reviews in Microbiology·Helioswilton Sales-CamposCarlo José Freire Oliveira
Nov 21, 2017·Biomedicine Hub·Richard InselJoseph Hedrick
Jul 17, 2020·Frontiers in Endocrinology·Marina PrimaveraFrancesco Chiarelli
Nov 11, 2020·Current Diabetes Reports·Jeniffer D Loaiza NaranjoEmma E Hamilton-Williams
Nov 19, 2020·Diabetes·Fernanda M C SodréLut Overbergh
Feb 5, 2021·Scientific Reports·Magdalena StaniszewskaAndrzej Gamian
Aug 26, 2018·Translational Research : the Journal of Laboratory and Clinical Medicine·Lian YiWei-Jun Qian
May 7, 2021·Frontiers in Immunology·Teresa Rodriguez-CalvoJessica L Dunne
Jun 7, 2021·Current Opinion in Endocrinology, Diabetes, and Obesity·Laura M Jacobsen, Desmond A Schatz
Aug 10, 2021·Pediatric Diabetes·Johnny LudvigssonUNKNOWN TRIGR Investigators

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Methods Mentioned

BETA
ELISA
genotyping
deamination

Software Mentioned

GraphPad
Prism
Magellan

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