A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes
ABSTRACT Aims/Introduction Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Journal of Diabetes Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jdi.14031 |
| _version_ | 1797738676388626432 |
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| author | Leonard C Harrison Esther Bandala‐Sanchez Helena Oakey Peter G Colman Kelly Watson Ki Wook Kim Roy Wu Emma E Hamilton‐Williams Natalie L Stone Aveni Haynes Rebecca L Thomson Peter J Vuillermin Georgia Soldatos William D Rawlinson Kelly J McGorm Grant Morahan Simon C Barry Richard O Sinnott John M Wentworth Jennifer J Couper Megan AS Penno the ENDIA Study Group |
| author_facet | Leonard C Harrison Esther Bandala‐Sanchez Helena Oakey Peter G Colman Kelly Watson Ki Wook Kim Roy Wu Emma E Hamilton‐Williams Natalie L Stone Aveni Haynes Rebecca L Thomson Peter J Vuillermin Georgia Soldatos William D Rawlinson Kelly J McGorm Grant Morahan Simon C Barry Richard O Sinnott John M Wentworth Jennifer J Couper Megan AS Penno the ENDIA Study Group |
| author_sort | Leonard C Harrison |
| collection | DOAJ |
| description | ABSTRACT Aims/Introduction Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically at‐risk for type 1 diabetes followed from birth who had developed islet autoantibodies (“seroconverted”), by measuring mucosa‐associated cytokines in their sera. Materials and Methods Sera were collected 3 monthly from birth from children with a first‐degree type 1 diabetes relative, in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Children who seroconverted were matched for sex, age, and sample availability with seronegative children. Luminex xMap technology was used to measure serum cytokines. Results Of eight children who seroconverted, for whom serum samples were available at least 6 months before and after seroconversion, the serum concentrations of mucosa‐associated cytokines IL‐21, IL‐22, IL‐25, and IL‐10, the Th17‐related cytokines IL‐17F and IL‐23, as well as IL‐33, IFN‐γ, and IL‐4, peaked from a low baseline in seven around the time of seroconversion and in one preceding seroconversion. These changes were not detected in eight sex‐ and age‐matched seronegative controls, or in a separate cohort of 11 unmatched seronegative children. Conclusions In a cohort of children at risk for type 1 diabetes followed from birth, a transient, systemic increase in mucosa‐associated cytokines around the time of seroconversion lends support to the view that mucosal infection, e.g., by an enteric virus, may drive the development of islet autoimmunity. |
| first_indexed | 2024-03-12T13:47:18Z |
| format | Article |
| id | doaj.art-993f04912a044005ba462f8d64f9e9e5 |
| institution | Directory Open Access Journal |
| issn | 2040-1116 2040-1124 |
| language | English |
| last_indexed | 2024-03-12T13:47:18Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Investigation |
| spelling | doaj.art-993f04912a044005ba462f8d64f9e9e52023-08-23T08:32:21ZengWileyJournal of Diabetes Investigation2040-11162040-11242023-09-011491092110010.1111/jdi.14031A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetesLeonard C Harrison0Esther Bandala‐Sanchez1Helena Oakey2Peter G Colman3Kelly Watson4Ki Wook Kim5Roy Wu6Emma E Hamilton‐Williams7Natalie L Stone8Aveni Haynes9Rebecca L Thomson10Peter J Vuillermin11Georgia Soldatos12William D Rawlinson13Kelly J McGorm14Grant Morahan15Simon C Barry16Richard O Sinnott17John M Wentworth18Jennifer J Couper19Megan AS Penno20the ENDIA Study GroupWalter and Eliza Hall Institute of Medical Research Melbourne Victoria AustraliaWalter and Eliza Hall Institute of Medical Research Melbourne Victoria AustraliaRobinson Research Institute and Adelaide Medical School University of Adelaide Adelaide South Australia AustraliaDepartment of Diabetes and Endocrinology Royal Melbourne Hospital Melbourne Victoria AustraliaDepartment of Diabetes and Endocrinology Royal Melbourne Hospital Melbourne Victoria AustraliaVirology Research Laboratory, Serology and Virology Division NSW Health, Prince of Wales Hospital Sydney New South Wales AustraliaVirology Research Laboratory, Serology and Virology Division NSW Health, Prince of Wales Hospital Sydney New South Wales AustraliaFrazer Institute The University of Queensland Brisbane Queensland AustraliaWalter and Eliza Hall Institute of Medical Research Melbourne Victoria AustraliaTelethon Kids Institute for Child Health Research, Centre for Child Health Research the University of Western Australia Perth Western Australia AustraliaRobinson Research Institute and Adelaide Medical School University of Adelaide Adelaide South Australia AustraliaFaculty of School of Medicine Deakin University Geelong Victoria AustraliaMonash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine Monash University Melbourne Victoria AustraliaVirology Research Laboratory, Serology and Virology Division NSW Health, Prince of Wales Hospital Sydney New South Wales AustraliaRobinson Research Institute and Adelaide Medical School University of Adelaide Adelaide South Australia AustraliaCentre for Diabetes Research, Harry Perkins Institute of Medical Research The University of Western Australia Perth Western Australia AustraliaRobinson Research Institute and Adelaide Medical School University of Adelaide Adelaide South Australia AustraliaMelbourne eResearch Group, School of Computing and Information Services University of Melbourne Melbourne Victoria AustraliaWalter and Eliza Hall Institute of Medical Research Melbourne Victoria AustraliaRobinson Research Institute and Adelaide Medical School University of Adelaide Adelaide South Australia AustraliaRobinson Research Institute and Adelaide Medical School University of Adelaide Adelaide South Australia AustraliaABSTRACT Aims/Introduction Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically at‐risk for type 1 diabetes followed from birth who had developed islet autoantibodies (“seroconverted”), by measuring mucosa‐associated cytokines in their sera. Materials and Methods Sera were collected 3 monthly from birth from children with a first‐degree type 1 diabetes relative, in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Children who seroconverted were matched for sex, age, and sample availability with seronegative children. Luminex xMap technology was used to measure serum cytokines. Results Of eight children who seroconverted, for whom serum samples were available at least 6 months before and after seroconversion, the serum concentrations of mucosa‐associated cytokines IL‐21, IL‐22, IL‐25, and IL‐10, the Th17‐related cytokines IL‐17F and IL‐23, as well as IL‐33, IFN‐γ, and IL‐4, peaked from a low baseline in seven around the time of seroconversion and in one preceding seroconversion. These changes were not detected in eight sex‐ and age‐matched seronegative controls, or in a separate cohort of 11 unmatched seronegative children. Conclusions In a cohort of children at risk for type 1 diabetes followed from birth, a transient, systemic increase in mucosa‐associated cytokines around the time of seroconversion lends support to the view that mucosal infection, e.g., by an enteric virus, may drive the development of islet autoimmunity.https://doi.org/10.1111/jdi.14031Islet autoantibodySeroconversionSerum cytokine |
| spellingShingle | Leonard C Harrison Esther Bandala‐Sanchez Helena Oakey Peter G Colman Kelly Watson Ki Wook Kim Roy Wu Emma E Hamilton‐Williams Natalie L Stone Aveni Haynes Rebecca L Thomson Peter J Vuillermin Georgia Soldatos William D Rawlinson Kelly J McGorm Grant Morahan Simon C Barry Richard O Sinnott John M Wentworth Jennifer J Couper Megan AS Penno the ENDIA Study Group A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes Journal of Diabetes Investigation Islet autoantibody Seroconversion Serum cytokine |
| title | A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes |
| title_full | A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes |
| title_fullStr | A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes |
| title_full_unstemmed | A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes |
| title_short | A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes |
| title_sort | surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes |
| topic | Islet autoantibody Seroconversion Serum cytokine |
| url | https://doi.org/10.1111/jdi.14031 |
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