title: Identification of novel autoantibodies in type 1 diabetic patients using a high-density protein microarray.
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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea Department of Internal Medicine, Boramae Medical Center, Seoul, Korea.
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Koo
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Sehyun
authors.initials: S
authors.lastname: Chae
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department 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.
authors.forename: Min Jueng
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
authors.forename: Eunhee G
authors.initials: EG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Soo Heon
authors.initials: SH
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Choong Ho
authors.initials: CH
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hak C
authors.initials: HC
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Chan Soo
authors.initials: CS
authors.lastname: Shin
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea Center for Systems Biology of Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea kspark@snu.ac.kr euyi@snu.ac.kr dhwang@dgist.ac.kr.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: Department 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 kspark@snu.ac.kr euyi@snu.ac.kr dhwang@dgist.ac.kr.
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Yi
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea Department 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 kspark@snu.ac.kr euyi@snu.ac.kr dhwang@dgist.ac.kr.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D020648:Peptide Elongation Factor 1 / Q000276:immunology; D040081:Protein Array Analysis; D044763:Ubiquitin-Conjugating Enzymes / Q000276:immunology
chemical_list: D001323:Autoantibodies; C094814:EEF1A1 protein, human; D020648:Peptide Elongation Factor 1; C079437:UBE2L3 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2