Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes

J Clin Invest. 1996 Jun 15;97(12):2772-83. doi: 10.1172/JCI118732.


Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. Here we identify a third islet cell autoantigen, a novel 38-kD protein, which is specifically immunoprecipitated with sera from a subset of prediabetic individuals and newly diagnosed type 1 diabetic patients. The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD65 and IA2. Removal of N-linked carbohydrates results in a protein of 22,000 Mr. Glima 38 autoantibodies were detected in 16/86 (19%) of newly diagnosed patients, including three very young children, who had a rapid onset of disease, and in 6/44 (14%) of prediabetic individuals up to several years before clinical onset. The cumulative incidence of GAD65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD65, glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. GAD65, IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Animals
  • Autoantibodies / analysis*
  • Autoantigens / analysis*
  • Cell Line
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Glutamate Decarboxylase / analysis*
  • Humans
  • Infant
  • Islets of Langerhans / immunology*
  • Male
  • Membrane Glycoproteins / analysis*
  • Membrane Proteins / analysis*
  • Mice
  • Molecular Weight
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / analysis*
  • Rats
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8


  • Autoantibodies
  • Autoantigens
  • Membrane Glycoproteins
  • Membrane Proteins
  • islet cell antibody
  • PTPRN protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Ptprn protein, mouse
  • Ptprn protein, rat
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase