Refereed journal article or data article (A1)

Primary islet autoantibody at initial seroconversion and autoantibodies at diagnosis of type 1 diabetes as markers of disease heterogeneity




List of AuthorsJorma Ilonen, Johanna Lempainen, Anna Hammais, Antti-Pekka Laine, Taina Härkönen, Jorma Toppari, Riitta Veijola, Mikael Knip

PublisherWILEY

Publication year2018

JournalPediatric Diabetes

Journal name in sourcePEDIATRIC DIABETES

Journal acronymPEDIATR DIABETES

Volume number19

Issue number2

Start page284

End page292

Number of pages9

ISSN1399-543X

DOIhttp://dx.doi.org/10.1111/pedi.12545

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/30084753


Abstract
Objective: The relationship between patterns of islet autoantibodies at diagnosis and specificity of the first islet autoantibody at the initiation of autoimmunity was analyzed with the aim of identifying patterns informative of the primary autoantibodies.Methods: Information about a single first autoantibody at seroconversion and autoantibody data at diagnosis were available for 128 children participating in the follow-up cohort of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study. Autoantibody data at diagnosis and genotyping results were also obtained from children in the Finnish Pediatric Diabetes Register (FPDR).Results: Insulin autoantibodies (IAA) were the most common primary antibodies (N = 68), followed by those for glutamic acid decarboxylase (GADA; N = 38), IA-2 antigen (IA-2A; N = 13), and zinc transporter 8 (ZnT8A; N = 9), whereas at diagnosis, IA-2A were most frequent (N = 103), followed by IAA (N = 78), ZnT8A (N = 73), and GADA (N = 71). Accordingly, the presence of many specific autoantibodies at diagnosis was due to the secondary antibodies appearing after primary antibodies, and in some cases, the primary autoantibody, most often IAA, had already disappeared at the time of diagnosis. Many of the autoantibody combinations present at diagnosis could be assembled into groups associated with either IAA or GADA as first autoantibodies. These combinations, in children diagnosed below the age of 10 years in the FPDR, were found to be strongly associated with risk genotypes in either INS (IAA first) or IKZF4-ERBB3 (GADA first) genes.Conclusions: Autoantibody patterns at diagnosis may be informative on primary autoantibodies initiating autoimmunity in young children developing type 1 diabetes.

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Last updated on 2022-07-04 at 16:48