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 ≤20 years) of short duration (≤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.
Pancreatic Islet Cell Cytoplasmic Antibody in Diabetes is Represented by Antibodies to Islet Cell Antigen 512 and Glutamic Acid Decarboxylase
ELISA, enzyme-linked immunosorbent assay; GAD, glutamic acid decarboxylase; GST, glutathione-S-transferase; ICA, islet cell antibody; IDDM, insulin-dependent diabetes mellitus; JDF U, Juvenile Diabetes Foundation units; OD, optical density; PBS, phosphate-buffered saline; SM, skim milk.
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Mark A Myers, Daniel U Rabin, Merrill J Rowley; Pancreatic Islet Cell Cytoplasmic Antibody in Diabetes is Represented by Antibodies to Islet Cell Antigen 512 and Glutamic Acid Decarboxylase. Diabetes 1 November 1995; 44 (11): 1290–1295. https://doi.org/10.2337/diab.44.11.1290
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