Avidity of Islet Cell Autoantibodies in Non-Diabetic Children and Children with Insulin-Dependent Diabetes

Abstract

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

Key Words:

• Insulin-dependent diabetes
• Islet cell autoantibodies
• Avidity
• Time-resolved fluorescence imaging
• Europium chelate