Avidity of islet cell autoantibodies in non-diabetic children and children with insulin-dependent diabetes.
Low-avidity immunoglobulin G antibodies, which commonly occur after microbial infections and form unstable complexes with the antigen, are within weeks replaced by high-avidity antibodies, which bind the antigen tightly and characterise mature immune response. We hypothesised that avidity of islet cell autoantibodies (ICA), found in the sera of patients with insulin-dependent diabetes mellitus (IDDM) usually months or years before disease onset, might reflect the stage of progression towards overt IDDM. ICA were quantitated before and after treatment of antigen-antibody complexes with 5 M urea in a new assay, in which the fluorescence intensity of europium chelate-labelled detecting antibody is measured from a digital time-resolved fluorescence image. The proportion of urea-resistant ICA of all ICA was defined as the avidity index. The median avidity indices (range) of 119 children with recent-onset IDDM and 64 non-diabetic ICA-positive children were 74% (23-100%) and 11% (0-100%), respectively (p = 0.0001). The avidity indices of only 3 children with IDDM (2.5%), but of 55 non-diabetic ICA-positive children (86%) were < 40%. In conclusion, our data show that ICA avidity indices of ICA-positive non-diabetic children and children with IDDM differ, suggesting that measurement of ICA avidity may improve prediction of the time of onset of clinical IDDM.
Rulli
M
M
Department of Paediatrics and MediCity Research Laboratory, University of Turku, Finland. marulli@utu.fi
Simell
O
O
D000293:Adolescent; D000915:Antibody Affinity / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology*
D001323:Autoantibodies; C024211:islet cell antibody