Time-Resolved Autoantibody Profiling Facilitates Stratification of Preclinical Type 1 Diabetes in Children.
In: Diabetes, Jg. 68 (2019), Heft 1, S. 119-130
academicJournal
Zugriff:
Progression to clinical type 1 diabetes varies among children who develop β-cell autoantibodies. Differences in autoantibody patterns could relate to disease progression and etiology. Here we modeled complex longitudinal autoantibody profiles by using a novel wavelet-based algorithm. We identified clusters of similar profiles associated with various types of progression among 600 children from The Environmental Determinants of Diabetes in the Young (TEDDY) birth cohort study; these children developed persistent insulin autoantibodies (IAA), GAD autoantibodies (GADA), insulinoma-associated antigen 2 autoantibodies (IA-2A), or a combination of these, and they were followed up prospectively at 3- to 6-month intervals (median follow-up 6.5 years). Children who developed multiple autoantibody types (n = 370) were clustered, and progression from seroconversion to clinical diabetes within 5 years ranged between clusters from 6% (95% CI 0, 17.4) to 84% (59.2, 93.6). Children who seroconverted early in life (median age <2 years) and developed IAA and IA-2A that were stable-positive on follow-up had the highest risk of diabetes, and this risk was unaffected by GADA status. Clusters of children who lacked stable-positive GADA responses contained more boys and lower frequencies of the HLA-DR3 allele. Our novel algorithm allows refined grouping of β-cell autoantibody-positive children who distinctly progressed to clinical type 1 diabetes, and it provides new opportunities in searching for etiological factors and elucidating complex disease mechanisms. [ABSTRACT FROM AUTHOR]
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Titel: |
Time-Resolved Autoantibody Profiling Facilitates Stratification of Preclinical Type 1 Diabetes in Children.
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Autor/in / Beteiligte Person: | Endesfelder, David ; Wolfgang zu Castell ; Bonifacio, Ezio ; Rewers, Marian ; Hagopian, William A. ; She, Jin‐Xiong ; Lernmark, Åke ; Toppari, Jorma ; Vehik, Kendra ; Williams, Alistair J. K. ; Yu, Liping ; Akolkar, Beena ; Krischer, Jeffrey P. ; Ziegler, Anette G. ; Achenbach, Peter ; Castell, Wolfgang Zu ; She, Jin-Xiong ; TEDDY Study Group ; Zu Castell, Wolfgang |
Zeitschrift: | Diabetes, Jg. 68 (2019), Heft 1, S. 119-130 |
Veröffentlichung: | 2019 |
Medientyp: | academicJournal |
ISSN: | 0012-1797 (print) |
DOI: | 10.2337/db18-0594 |
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