PANCREATIC-ISLET CELL CYTOPLASMIC ANTIBODY IN DIABETES IS REPRESENTED BY ANTIBODIES TO ISLET-CELL ANTIGEN-512 AND GLUTAMIC-ACID DECARBOXYLASE

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 (GAD(65)) 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 GAD(65). 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 less than or equal to 20 years) of short duration (less than or equal to 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.