Identification of Novel Autoantibodies in Type 1 Diabetic Patients Using a High-Density Protein Microarray

  1. Kyong Soo Park1,5
  1. 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
  2. 2Department of Internal Medicine, Boramae Medical Center, Seoul, Korea
  3. 3School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea
  4. 4Department of Systems Immunology, College of Biomedical Science, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea
  5. 5Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea
  6. 6Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
  7. 7Center for Systems Biology of Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea
  1. Corresponding authors: Daehee Hwang, dhwang{at}dgist.ac.kr; Eugene C. Yi, euyi{at}snu.ac.kr; or Kyong Soo Park, kspark{at}snu.ac.kr.

Abstract

Autoantibodies can facilitate diagnostic and therapeutic means for type 1 diabetes (T1DM). We profiled autoantibodies from serum samples of 16 T1DM patients, 16 type 2 diabetic (T2DM) patients, and 27 healthy control subjects with normal glucose tolerance (NGT) by using protein microarrays containing 9,480 proteins. Two novel autoantibodies, anti-EEF1A1 and anti-UBE2L3, were selected from microarrays followed by immunofluorescence staining of pancreas. We then tested the validity of the candidates by ELISA in two independent test cohorts: 1) 95 adults with T1DM, 49 with T2DM, 11 with latent autoimmune diabetes in adults (LADA), 20 with Graves disease, and 66 with NGT and 2) 33 children with T1DM and 34 healthy children. Concentrations of these autoantibodies were significantly higher in T1DM patients than in NGT and T2DM subjects (P < 0.01), which was also confirmed in the test cohort of children (P < 0.05). Prevalence of anti-EEF1A1 and anti-UBE2L3 antibodies was 29.5% and 35.8% in T1DM, respectively. Of note, 40.9% of T1DM patients who lack anti-GAD antibodies (GADA) had anti-EEF1A1 and/or anti-UBE2L3 antibodies. These were also detected in patients with fulminant T1DM but not LADA. Our approach identified autoantibodies that can provide a new dimension of information indicative of T1DM independent of GADA and new insights into diagnosis and classification of T1DM.

Footnotes

  • B.K.K., S.C., K.M.K, and M.J.K. contributed equally to this work.

  • Received October 14, 2013.
  • Accepted April 11, 2014.

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