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

• Published in: Pediatric diabetes Vol. 19; no. 2; pp. 284 - 292
• Main Authors: Ilonen, Jorma, Lempainen, Johanna, Hammais, Anna, Laine, Antti‐Pekka, Härkönen, Taina, Toppari, Jorma, Veijola, Riitta, Knip, Mikael
• Format: Journal Article
• Language: English
• Published: Former Munksgaard John Wiley & Sons A/S 01.03.2018; Wiley Subscription Services, Inc
• Subjects: Autoantibodies; Autoimmunity; Children; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diagnosis; disease heterogeneity; ErbB-3 protein; genetics; Genotypes; Genotyping; Glutamate decarboxylase; Glutamic acid; Immunoglobulins; Insulin; islet autoantibodies; Medical diagnosis; Seroconversion; type 1 diabetes; Zinc transporter; type 1 diabetes; genetics; islet autoantibodies; disease heterogeneity
• ISSN: 1399-543X; 1399-5448
• DOI: 10.1111/pedi.12545

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.