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Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
University of Campus Biomed Roma, Italy.
University of Campus Biomed Roma, Italy; Queen Mary University of London, England.
University of Campus Biomed Roma, Italy; IRCCS Ist Ortoped Galeazzi, Italy.
University of Campus Biomed Roma, Italy; Queen Mary University of London, England.
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2017 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 8, p. 1467-1474Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis 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. Methods 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 insulinmodified by (OH)-O-center dot or HOCl were measured by our developed ELISA platform. Results Antibodies to at least one oxPTM-INS were present in 91.3% of progr-T1D children. oxPTM-INS-Ab co-existed with GADA, IA-2A, IAA or ZnT8A in 65.2%, 56.5%, 38.9% and 33.3% progr-T1D children, respectively. In addition, oxPTM-INS-Ab were present in 17.4%, 26.1%, 38.9% and 41.6% of progr-T1D children who were negative for GADA, IA-2A, IAA and ZnT8A, respectively. (OH)-O-center dot-INS-Ab were more common in progr-T1D children than in NP-AAB+ children (82.6% vs 19%; p amp;lt; 0.001) and allowed discrimination between progr-T1D and NP-AAB(+) children with 74% sensitivity and 91% specificity. None of the NP-AAB(-) children were positive for oxPTM-INS-Ab. Conclusions/interpretation oxPTM-INS-Ab are present before the clinical onset of type 1 diabetes and can identify children progressing to type 1 diabetes.

Place, publisher, year, edition, pages
SPRINGER , 2017. Vol. 60, no 8, p. 1467-1474
Keywords [en]
Biomarker; Insulin; Insulin autoantibodies; Islet autoantibodies; Oxidative stress; Post-translational modifications; Type 1 diabetes
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:liu:diva-139384DOI: 10.1007/s00125-017-4296-1ISI: 000404354900012PubMedID: 28526919OAI: oai:DiVA.org:liu-139384DiVA, id: diva2:1129826
Note

Funding Agencies|EFSD/JDRF/Lilly European Programme [3-PAR-2016-277-A-N]; JDRF innovative grant [INO-2015-78-S-B]; Swedish Research Council [K2005-72X-11242-11A, K2008-69X-20826-01-4]; Swedish Child Diabetes Foundation (Barndiabetesfonden); JDRF Wallenberg Foundation [K 98-99D-12813-01A]; Medical Research Council of Southeast Sweden (FORSS); Swedish Council for Working Life and Social Research [FAS2004-1775]

Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2017-08-27

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Division of Children's and Women's healthFaculty of Medicine and Health SciencesDepartment of Paediatrics in Linköping
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