Islet Autoantibody Seroconversion in the DPT-1 Study: Justification for repeat screening throughout childhood

Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida, USA.
Diabetes care (Impact Factor: 8.42). 02/2011; 34(2):358-62. DOI: 10.2337/dc10-1494
Source: PubMed


Although type 1 diabetes autoimmunity frequently begins in childhood, little is known about the relationship between age and autoimmunity development. Our aim was to determine the timing of seroconversion to diabetes-associated autoantibody (DAA) positivity and risk in first- and second-degree relatives of patients with type 1 diabetes.
Study subjects were identified through the Diabetes Prevention Trial-Type 1 (DPT-1). Children 3-18 years of age (n = 42,447) were screened for DAAs; 1,454 were ICA positive (≥ 10 JDF units), 1,758 were GAD65 positive, and 899 were ICA512 positive at the time of initial screening. Subjects who were initially antibody negative (n = 39,212) were recalled for rescreening, and 11,813 returned for rescreening.
DAA seroconversion occurred in 469 (4%) children; 258 seroconverted to ICA, 234 to GAD65, and 99 to ICA512. The median time to seroconversion was 2 years. The 2-year risk for DAAs was highest in early childhood. For each 1-year increase in age in this cohort, the risk of any autoantibody seroconversion (HR 0.95, 95% CI 0.92-0.97) decreased by 5%, and for any two autoantibodies risk decreased by 13% (0.87, 0.82-0.93).
Risk of autoantibody seroconversion among children followed in DPT-1 is age dependent. Younger children have the highest risk for DAAs, with the majority of children seroconverting by 13 years of age (75%). This suggests that annual screenings should be started in early childhood and continued through early adolescence to identify the majority of subjects at risk for type 1 diabetes and eligible for prevention trials.

Download full-text


Available from: Michael Haller
  • Source
    • "Type 1 diabetes (T1D) is characterized by immune-mediated destruction of the insulin-secreting í µí»½ cells in the pancreatic islets as a result of an unknown trigger mechanism. It is, however, well known that development of clinical disease is preceded by an asymptomatic latent period during which immune reactions against the insulin-secreting cell autoantigens can be demonstrated [1] [2] [3]. In this context, biochemically detectable autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma-associated antigen 2 (IA-2A), and Zn-transporter 8 (ZnT8A) as well as their counterpart immunofluorescent anti-islet antibodies (ICA) serve as reliable biomarkers for T1D development. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The intestinal microbiota is essential to the maturation and homeostasis of the immune system. Immunoblot assays were used to establish the prevalence of serum IgG, IgM, and IgA antibodies specific for Bifidobacterium adolescentis, Bifidobacterium longum, and Lactobacillus rhamnosus GG proteins in young children presenting with or without type 1 diabetes (T1D). We demonstrated that children between the ages of 6 and 12 months had a substantial increase in the frequency of IgG antibodies specific for L. rhamnosus GG proteins. We measured IgG, IgM, and IgA class antibody reactivity against B. adolescentis DSM 20083, B. adolescentis DSM 20086, and B. longum DSM 20088 proteins demonstrating significantly higher IgA responses against B. adolescentis DSM 20083 strain proteins in children who developed islet autoimmunity and T1D later in life. B. adolescentis strains showed more IgM type antibodies in children who developed T1D later in life, but the difference was not statistically significant. B. longum proteins were recognized by IgG and IgA antibodies to a higher extent compared to other bacteria studied. These results confirm that differences in immune reactivity against some commensal strains in young children may represent a different risk factor for developing T1D.
    Full-text · Article · Mar 2014 · Journal of Immunology Research
  • Source
    • "Knip et al. (3) reported that, in the general population in Finland, β-cell autoimmunity can be induced at any age. In the Diabetes Prevention Trial–Type 1 (DPT-1) study involving relatives with type 1 diabetes, we recently reported that seroconversion declines with age and extends throughout childhood and early adulthood (2). We found that GAD65 and ICA had the highest 2-year seroconversion risks, with GAD65 having the greatest risk in the very young (≤6 years of age). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the relationship between age and islet autoantibody (Ab) seroconversion can establish the optimal screening interval(s) to assess risk for type 1 diabetes, identify subjects who can participate in prevention trials, and determine associated costs. This study assessed the rates of seroconversion to glutamic acid decarboxylase positive (GAD65(+)), insulin positive (mIAA(+)), and insulinoma-associated protein 2 positive (ICA512(+)) in a large cohort of relatives of type 1 diabetes probands undergoing Ab rescreening in the TrialNet Natural History Study. Of 32,845 children aged <18 years screened for Abs, 1,287 (3.9%) were GAD65(+), 778 (2.4%) were mIAA(+), 677 (2.1%) were ICA512(+), and 31,038 were Ab-negative. Ab-negative children were offered annual rescreening up to 18 years of age. Cox regression was used to estimate the risk for GAD65, mIAA, and ICA512 seroconversion. RESULTS There were 205 children who seroconverted to GAD65(+), 155 who seroconverted to mIAA(+), and 53 who seroconverted to ICA512(+) over 5.8 years of follow-up. The risk of mIAA (hazard ratio 0.89 [95% CI 0.85-0.92]) and GAD65 (0.96 [0.93-0.99]) seroconversion significantly decreased with increasing age (i.e., for each 1-year increase in age, the risk of seroconversion decreased by 11% [P < 0.0001] for mIAA and 4% [P = 0.04] for GAD65) across all ages. The cumulative Ab seroconversion was 2% for those <10 years of age versus 0.7% for those ≥10 years of age. The risk of development of islet Abs declines with increasing age in type 1 diabetes relatives. These data support annual screening for children <10 years of age and one additional screening in adolescence.
    Full-text · Article · Jul 2011 · Diabetes care
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Autoantibody against interferon is associated in many viral and non-viral diseases. This study aimed to determine the prevalence of anti-IFN-alpha autoantibodies in healthy Egyptian blood donors. The study included 558 (100 females (17.92%) and 458 males (82.08%)) Egyptian healthy blood donors who showed normal levels of liver enzymes and kidney tests and were conformed negative for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Abs), HIV-1/2 Abs, anti-HBc and Treponema Abs. Autoantibody against IFN-alpha-1a and IFN-alpha-2b were screened using ELISA. Anti-IFN-alpha-1a positive cases were found to be 43 subject (7.76%; 6 females (1.08%); 37 males (6.68%)) and anti-IFN-alpha-2b positive cases were found to be 3 (0.54%; all males). Combined positivity against both IFN-alpha-1a and IFN-alpha-2b was 38 (6.86%; 7 females (1.26%) and 31 males (6.60%)). From these findings we can conclude that antibodies against IFN-alpha are present in considerable number at low titer in accepted blood donors.
    Full-text · Article · Aug 2011 · Cellular Immunology
Show more