Pancreatic islet cell cytoplasmic antibody in diabetes is represented by antibodies to islet cell antigen 512 and glutamic acid decarboxylase

Abstract

The presence of serum islet cell cytoplasmic antibodies (ICAs) is a standard autoimmune marker for insulin-dependent diabetes mellitus (IDDM). The antigenic molecule(s) responsible for ICA has not been identified, although antibodies to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) do contribute. We tested 129 IDDM sera for antibodies to ICA512 (anti-ICA512), antibodies to GAD (anti-GAD), and ICAs; we tested for inhibition of ICAs with purified recombinant ICA512 and sheep brain GAD; and we tested for immunofluorescence reactivity on COS7 cells transfected with cDNA clones encoding ICA512 and GAD65. The results were that anti-ICA512 antibodies contribute to ICA reactivity and that these, in combination with anti-GAD antibodies, account for most ICA reactivity in IDDM. Anti-ICA512 antibodies were present at a frequency of 51% in 61 patients with early-onset IDDM (age of onset < or = 20 years) of short duration (< or = 1 month) but only in 9% of 68 patients with an onset age of > 20 years and/or a disease duration of > 1 month. The frequency of anti-GAD antibodies in these sera was similar irrespective of duration or age of onset. Anti-ICA512 and anti-GAD antibodies were demonstrable by indirect immunofluorescence on transfected COS7 cells, and ICA could be inhibited using either recombinant ICA512 or purified brain GAD. We conclude that anti-ICA512 and anti-GAD antibodies contribute to ICA reactivity and that anti-ICA512 antibodies account for the increased frequency of ICA reactivity in early-onset IDDM of short duration.