Anti-glutamate decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study

Abstract

Summary Sera obtained at diagnosis from 273 children (0-14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75 % of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment > 99% complete). Antibodies against glutamate decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme-linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-glutamate decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69 % were positive for anti-glutamate decarboxylase, 65 % for insulin autoantibodies, 71% for islet cell antibodies (>/20 Juvenile Diabetes Foundation units), 10 % for anti-thyroid peroxidase, 2.6 % for antigliadin and 3.0 % for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7 % of the sera, while only 5.8 % were negative for all three of islet cell antibodies, insulin autoantibodies and anti-glutamate decarboxylase. There was a higher frequency of anti-glutamate decarboxylase among girls than boys (75 % vs 63 %, p = 0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r =-0.41, p < 0.0001). A higher frequency of antithyroid peroxidase was found with increasing age (p = 0.05). Higher titres of islet cell antibodies were associated with a higher frequency of both anti-glutamate decarboxylase (p < 0.0001) and insulin autoantibodies (p = 0.003). Five children (1.8 %) with clear elevations of antigliadin and anti-endomysial antibodies were found to have asymptomatic coeliac disease by small bowel biopsy. [Diabetologia (1994[Diabetologia ( ) 37: 1113[Diabetologia ( -1120

HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study in Sweden

“…Our study also confirmed that IA-2A were associated with male gender, whereas GADA presence and high levels were associated with female gender [37,38]. However, logistic regression analysis showed that the associations between gender and age at onset to the types of islet antibodies were not related to risk HLA-DQB1 genotypes, as indeed previously shown [39].…”

Flow cytometric microsphere-based immunoassay as a novel non-radiometric method for the detection of glutamic acid decarboxylase autoantibodies in type 1 diabetes mellitus

“…a), observing a considerable number of borderline sera. Thus, the reference method demonstrated a representative prevalence of 72.5% in this population (percentage of Type 1 diabetic patients GADA positive from the total population studied), in agreement with previous reports (70-80%) 5,[33][34][35][36] . On the other hand, 17 GADA positive sera by RBA scored positive when evaluated by ELISA, whereas 23 patients were negative (Fig.…”

Autoimmune diagnostics in diabetes mellitus

“…Autoantibodies to tyrosine phosphatase IA-2 (IA2-Ab) are present in 50-70% of children and adolescents and in 30-50% of adults at the manifestation of type 1 diabetes (6,8,10,11). The most sensitive detection can be achieved by RIAs using human recombinant antigen.…”

“…In older patients, IAAs are present in only 20-30% (7,8,10,13). The detection of IAAs should be carried out using RIA, because ELISAs have been shown to possess significantly reduced sensitivity and specificity (14).…”