Dynamics of Diabetes-Associated Autoantibodies in Young Children with Human Leukocyte Antigen-Conferred Risk of Type 1 Diabetes Recruited from the General Population

Abstract

This study characterized the dynamics of islet cell antibodies (ICA), insulin antibodies (IAA), glutamic acid decarboxylase antibodies (GADA), and IA-2 antibodies (IA-2A) in 1006 children recruited from the general population due to human leukocyte antigen (HLA) DQB1-conferred risk for type 1 diabetes (T1D). By the age of 5 yr, 13.8% of the children had had one or more autoantibodies in at least one sample drawn at 3- to 12-month intervals from birth, whereas 6.1% had had one or more of the three autoantibodies to biochemically defined antigens in at least two consecutive samples. The cumulative frequencies of positivity for at least two antibodies ranged from 3.2-4.4%. Seventy-five children (7.5%) had at least once ICA, 83 (8.3%) had IAA, 46 (4.6%) had GADA, and 33 (3.3%) had IA-2A. IAA were transient more frequently than the other antibodies (P < or = 0.03) and fluctuated between positivity and negativity more often than ICA (P = 0.001). The genetically high risk children were positive for each autoantibody reactivity more often (P < or = 0.03) than the moderate risk subjects. Thirteen of the 1006 children (1.3%) presented with T1D by the age of 5 yr. The most sensitive predictors of T1D were ICA and IAA, whereas the most specific predictor was IA-2A. Positivity for at least two autoantibodies of IAA, GADA, and IA-2A had the highest positive predictive value for T1D (34%). We conclude that the frequency of various diabetes-associated autoantibodies increases at a relatively stable rate at least up to the age of 5 yr. Persistent positivity for two or more autoantibodies appears to reflect destructive progressive beta-cell autoimmunity, whereas positivity for a single autoantibody may represent harmless nonprogressive or even regressive beta-cell autoimmunity.

Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

“…The autoantibodies were measured in the Research Laboratory, Department of Pediatrics, University of Oulu. ICA, IAA, GADA and IA-2A were quantified as described previously [21].…”

Analysis of pancreas tissue in a child positive for islet cell antibodies

“…The detection limit was 2.5 JDFU, and the disease sensitivity 100% and the specificity 98% in the most relevant standardisation round [14]. Insulin autoantibodies (IAA), GAD antibodies (GADA) and islet antigen 2 antibodies (IA-2A) were analysed with specific radio-binding assays as described [15]. The cut-off limits were based on the 99th percentile in more than 370 non-diabetic children and corresponded to 3.48 relative units (RU) for IAA, 5.36 RU for GADA and 0.43 RU for IA-2A.…”

Live attenuated enterovirus vaccine (OPV) is not associated with islet autoimmunity in children with genetic susceptibility to type 1 diabetes: prospective cohort study

“…Participants This study was carried out in a birth cohort of the ongoing prospective Type 1 Diabetes Prediction and Prevention (DIPP) study in Tampere, Finland, as previously described [15,16]. Briefly, all babies whose parents gave informed consent to participate in the study were first screened for HLA class II alleles conferring susceptibility to type 1 diabetes (HLA type was analysed from cord blood) and those with increased risk were recruited to the prospective follow-up study [15,16].…”

“…Briefly, all babies whose parents gave informed consent to participate in the study were first screened for HLA class II alleles conferring susceptibility to type 1 diabetes (HLA type was analysed from cord blood) and those with increased risk were recruited to the prospective follow-up study [15,16]. A group of 64 children (34 boys) from the DIPP study whose parents consented to the OPV trial presented here were vaccinated using four serial doses of OPV (Polio Sabin, SB Biologicals, Rixensart, Belgium) at the age of 2, 3, 6 and 12 months (two drops in each oral dose).…”

“…Islet autoantibodies were analysed from serum or plasma and included insulin autoantibodies (IAA), islet cell antibodies (ICA), insulinoma-associated protein 2 antibodies (IA-2A) and GAD antibodies (GADA) as previously described [16,18]. Positivity for multiple autoantibodies was defined as positivity for at least two of these autoantibodies during the whole follow-up period.…”