Transient antiislet autoantibodies: Infrequent occurrence and lack of association with "genetic" risk factors

We hypothesized that genetic determinants of expression of persistent antii slet autoantibodies would similarly influence the expression of transient a utoantibodies. To test this hypothesis, we prospectively evaluated sera fro m 478 relatives (SOC: sibling-offspring cohort) of patients with type 1 dia betes as well as 793 newborns from the general population (NEC: newborn non relative cohort) selected for expression of specific human leukocyte antige n haplotypes. Eight relatives of 478 (1.7% of SOC) expressed a transient autoantibody, an d none had the high risk genotype DR3/4(DQ2/8). In contrast, 28 relatives ( 5.9% had persistent antiislet autoantibodies, and 14 (50%) were DR3/4LDQ2/8 ) heterozygotes. Thirteen children of 793 (1.6% of NEC) expressed a transie nt autoantibody, and none had the high risk genotype DR3/4(DQ2/8). Seven of the NEC (0.9%) had persistent antiislet autoantibodies, and 4 (57.1%) were DR3/4(DQ2/8) heterozygous. Expression of persistent autoantibodies was strongly related to human leuko cyte antigen status and family history of type 1 diabetes. In contrast, the expression of transient antiislet autoantibodies did not differ by family history of diabetes, and none of the DR3/4(DQ2/8) relatives and DR3/4(DQ2/8 ) newborns expressed transient autoantibodies. Our results indicate that children can express transient antiislet autoanti bodies, but such transient autoantibodies are relatively infrequent and are not correlated with known genetic risk factors for type 1 diabetes.