Is Presence of Islet Autoantibodies at Birth Associated With Development of Persistent Islet Autoimmunity?

Abstract

OBJECTIVE -To determine whether the presence of islet autoantibodies in the umbilical cord blood is predictive of subsequent development of islet autoimmunity. RESEARCH DESIGN AND METHODS-Cord blood sera from 1,118 subjects from the Diabetes Autoimmunity Study in the Young (DAISY) cohort, as well as their venous blood samples taken at follow-up clinic visits, were tested for GAD65 autoantibodies (GAAs), insulin autoantibodies (IAAs), and IA-2 autoantibodies (IA-2As). Venous blood samples taken from mothers of cord blood autoantibody-positive children were analyzed for the same autoantibodies.RESULTS -At least one of three islet autoantibodies was present in 42 (3.7%) of the cord blood samples tested. The presence of cord blood autoantibodies did not predict the subsequent development of islet autoimmunity (adjusted hazard ratio ϭ 0. 73 [0.09, 5.88]). Discordance between cord blood and corresponding maternal autoantibodies was seen in 3 of 36 infants. A strong correlation between levels of autoantibody in cord blood and maternal circulation was found for GAA (r 2 ϭ 0.93, P Ͻ 0.001) and IAA (r 2 ϭ 0.89, P Ͻ 0.001) but not IA-2A (r 2 ϭ 0.05, P ϭ 0.19). Cord blood autoantibodies in all but one subject disappeared by 9 months of age.CONCLUSIONS -The presence of cord blood autoantibodies is not predictive of subsequent development of islet autoimmunity. The majority of cord blood autoantibodies appear to result from maternal transmission. Diabetes Care 27:497-502, 2004T ype 1 diabetes is usually preceded by the presence of autoantibodies directed toward pancreatic islet cell antigens. The principle autoantibodies found to be associated with type 1 diabetes include GAD65 autoantibodies (GAAs), IA-2 autoantibodies (IA-2As), and insulin autoantibodies (IAAs) (1). These antibodies can be present months to years before the actual clinical diagnosis of diabetes and can serve as predictive markers of type 1 diabetes (2-5). In some children, islet autoantibodies can be detected in the umbilical cord blood. Although maternal transmission of islet autoantibodies to the newborn is not uncommon (6 -9), it has been suggested that not all autoantibodies found in cord blood result from transplacental transfer, but may instead result from in utero production of diabetes-associated autoantibodies (7,10,11).The relationship of cord blood autoantibodies and islet autoimmunity has been explored in previous studies (12-15). However, to assess the predictive value of cord blood autoantibodies in newborns, large prospective studies would be most useful. Since 1993, the Diabetes Autoimmunity Study in the Young (DAISY) has been prospectively investigating the natural history of islet autoimmunity (IA) in infants and children who are at a moderate to high risk of developing type 1 diabetes. Because of the high predictive value of islet autoantibodies, they can be used as a surrogate end point for type 1 diabetes research. This study was able to take advantage of a large bank of stored cord blood sera from DAISY participants, prospectively foll...

Evidence for immunological priming and increased frequency of CD4+ CD25+ cord blood T cells in children born to mothers with type 1 diabetes

“…As demonstrated here and in previous studies of our own [34,35], as well as of others [36][37][38], GADA in the fetus arise mainly because of the transplacental passage. We therefore propose the hypothesis that the immunological changes observed in the cord blood of neonates born to mothers with T1D may be due to GAD65 autoantibodies per se.…”

Natural History of Type 1 Diabetes

“…Consistent with this observation is the overall decreased risk to develop islet autoimmunity and diabetes in offspring of mothers with type 1 diabetes compared with that of offspring of fathers with type 1 diabetes and nondiabetic mothers (64,65). Data from the DAISY study was consistent with the findings from the BABYDIAB study in that the presence of cord blood islet autoantibodies was not predictive of subsequent development of islet autoimmunity in children who had diabetes-susceptible HLA genotypes (66).…”

Cord blood insulinoma-associated protein 2 autoantibodies are associated with increased risk of type 1 diabetes in the population-based Diabetes Prediction in Skåne study

“…In offspring to T1D mothers, cord blood autoantibodies have been reported to increase the risk for the child to develop the disease [10], but also to be of no effect [4] or even protective [3]. In a retrospective casecontrol study of cord blood sera from children diagnosed before the age of 15, cord blood autoantibodies was reported to increase the risk for the child to develop T1D, also after excluding T1D mothers.…”

“…Previous studies, mainly recruiting children with first-degree relatives with T1D, have investigated the significance of cord blood autoantibodies with contradictory results [3,4].…”