Primary islet autoantibody at initial seroconversion and autoantibodies at diagnosis of type 1 diabetes as markers of disease heterogeneity
2018
Objective The relationship between patterns of islet
autoantibodiesat diagnosis and specificity of the first islet
autoantibodyat the initiation of autoimmunity was analyzed with the aim of identifying patterns informative of the primary
autoantibodies. Methods Information about a single first
autoantibodyat seroconversion and
autoantibodydata at diagnosis were available for 128 children participating in the follow-up cohort of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study.
Autoantibodydata 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 transporter8 (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
autoantibodiesat 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
autoantibodycombinations 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
Autoantibodypatterns at diagnosis may be informative on primary
autoantibodiesinitiating autoimmunity in young children developing type 1 diabetes.
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