title: 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.
authors.affiliation: Centre for Molecular Biology and Medicine, Monash University, Victoria, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Myers
authors.forename: D U
authors.initials: DU
authors.lastname: Rabin
authors.forename: M J
authors.initials: MJ
authors.lastname: Rowley
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis / Q000097:blood*; D001324:Autoantigens; D001921:Brain / Q000276:immunology; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D012016:Reference Values; D012756:Sheep; D014162:Transfection
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D008565:Membrane Proteins; D011994:Recombinant Proteins; C024211:islet cell antibody; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase