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Pediatr Diabetes. 2018 Mar;19(2):284-292. doi: 10.1111/pedi.12545. Epub 2017 Jun 9.

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

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Immunogenetics Laboratory, University of Turku and Turku University Hospital, Turku, Finland.
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
Department of Pediatrics, Research Unit for Pediatrics, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
Folkhälsan Research Institute, Helsinki, Finland.
Department of Pediatrics, Tampere University Hospital, Tampere, Finland.



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.


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).


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.


Autoantibody patterns at diagnosis may be informative on primary autoantibodies initiating autoimmunity in young children developing type 1 diabetes.


disease heterogeneity; genetics; islet autoantibodies; type 1 diabetes

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