Islet autoimmunity in infants with a Type I diabetic relative is common but is frequently restricted to one autoantibody

Aims/hypothesis. To determine the sequence of development of islet autoanti bodies and their relation to HLA genes in infants at risk for Type I diabet es followed from birth. Methods. We followed 357 (189 male, 168 female) infants, with a first degre e relative with Type I diabetes for a mean of 3 years from birth. Human leu kocyte antigen typing and assays for insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADAb) and tyrosine phosphatase IA2 (IA2Ab) antibodies were done on cord blood, and venous blood was sampled every 6 m onths for IAA, GADAb and IA2Ab. Results. We did not find any antibodies in 263 (73 %) infants; 50 (14 %) we re positive for a single antibody once, 19 (5 %) for a single antibody more than once and 25 (7 %) for two or more antibodies. Of the latter, 10 (2.8 % overall) were persistently positive; they had higher frequencies of HLA D R4 (p < 0.01) and HLA DR3, 4 (p < 0.05). Of the group persistently positive for two or more antibodies four infants developed diabetes. Insulin autoan tibodies were the first ones to develop in 64 % of infants with two or more antibodies. Conclusion/interpretation. Infants with high risk HLA-DR alleles and multip le antibodies at high risk for diabetes were identified. A much larger grou p of infants had transient low level increases usually of a single antibody . Whereas transient low level positivity could be attributed to difficultie s with assay technique and cut off levels for normality, the results overal l support the phenomenon of transient 'self limited' islet autoimmunity in at risk infants.