PMID- 34747488
OWN - NLM
STAT- MEDLINE
DCOM- 20220302
LR  - 20220302
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 107
IP  - 3
DP  - 2022 Feb 17
TI  - Autoantibodies to N-terminally Truncated GAD65(96-585): HLA Associations and 
      Predictive Value for Type 1 Diabetes.
PG  - e935-e946
LID - 10.1210/clinem/dgab816 [doi]
AB  - OBJECTIVE: To evaluate the role of autoantibodies to N-terminally truncated 
      glutamic acid decarboxylase GAD65(96-585) (t-GADA) as a marker for type 1 
      diabetes (T1D) and to assess the potential human leukocyte antigen (HLA) 
      associations with such autoantibodies. DESIGN: In this cross-sectional study 
      combining data from the Finnish Pediatric Diabetes Register, the Type 1 Diabetes 
      Prediction and Prevention study, the DIABIMMUNE study, and the Early Dietary 
      Intervention and Later Signs of Beta-Cell Autoimmunity study, venous blood 
      samples from 760 individuals (53.7% males) were analyzed for t-GADA, 
      autoantibodies to full-length GAD65 (f-GADA), and islet cell antibodies. 
      Epitope-specific GAD autoantibodies were analyzed from 189 study participants. 
      RESULTS: T1D had been diagnosed in 174 (23%) participants. Altogether 631 (83%) 
      individuals tested positive for f-GADA and 451 (59%) for t-GADA at a median age 
      of 9.0 (range 0.2-61.5) years. t-GADA demonstrated higher specificity (46%) and 
      positive predictive value (30%) for T1D than positivity for f-GADA alone (15% and 
      21%, respectively). Among participants positive for f-GADA, those who tested 
      positive for t-GADA carried more frequently HLA genotypes conferring increased 
      risk for T1D than those who tested negative for t-GADA (77% vs 53%; P < 0.001). 
      CONCLUSIONS: Autoantibodies to N-terminally truncated GAD improve the screening 
      for T1D compared to f-GADA and may facilitate the selection of participants for 
      clinical trials. HLA class II-mediated antigen presentation of 
      GAD(96-585)-derived or structurally similar peptides might comprise an important 
      pathomechanism in T1D.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Pollanen, Petra M
AU  - Pollanen PM
AUID- ORCID: 0000-0001-7632-3293
AD  - Pediatric Research Center, Children's Hospital, University of Helsinki and 
      Helsinki University Hospital, Helsinki, Finland.
AD  - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, 
      University of Helsinki, Helsinki, Finland.
FAU - Harkonen, Taina
AU  - Harkonen T
AD  - Pediatric Research Center, Children's Hospital, University of Helsinki and 
      Helsinki University Hospital, Helsinki, Finland.
AD  - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, 
      University of Helsinki, Helsinki, Finland.
FAU - Ilonen, Jorma
AU  - Ilonen J
AUID- ORCID: 0000-0002-9973-2062
AD  - Immunogenetic Laboratory, Institute of Biomedicine, University of Turku, Turku, 
      Finland.
FAU - Toppari, Jorma
AU  - Toppari J
AUID- ORCID: 0000-0003-2228-334X
AD  - Department of Pediatrics, Turku University Hospital, and Institute of Biomedicine 
      and Centre for Population Health Research, University of Turku, Turku, Finland.
FAU - Veijola, Riitta
AU  - Veijola R
AD  - Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu 
      University Hospital and University of Oulu, Oulu, Finland.
FAU - Siljander, Heli
AU  - Siljander H
AD  - Pediatric Research Center, Children's Hospital, University of Helsinki and 
      Helsinki University Hospital, Helsinki, Finland.
AD  - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, 
      University of Helsinki, Helsinki, Finland.
FAU - Knip, Mikael
AU  - Knip M
AUID- ORCID: 0000-0003-0474-0033
AD  - Pediatric Research Center, Children's Hospital, University of Helsinki and 
      Helsinki University Hospital, Helsinki, Finland.
AD  - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, 
      University of Helsinki, Helsinki, Finland.
AD  - Tampere Center for Child Health Research, Tampere University Hospital, Tampere, 
      Finland.
LA  - eng
GR  - 1-SRA-2016-342-M-R/JDRF/Juvenile Diabetes Research Foundation/United States
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptide Fragments)
RN  - EC 4.1.1.- (GAD65 (96-585))
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antigen Presentation/genetics
MH  - Autoantibodies/*blood/immunology
MH  - Child
MH  - Child, Preschool
MH  - Clinical Trials as Topic
MH  - Cross-Sectional Studies
MH  - Diabetes Mellitus, Type 1/blood/*epidemiology/genetics/immunology
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotyping Techniques
MH  - Glutamate Decarboxylase/*immunology
MH  - Histocompatibility Antigens Class II/*genetics/metabolism
MH  - Humans
MH  - Infant
MH  - Male
MH  - Middle Aged
MH  - Patient Selection
MH  - Peptide Fragments/*immunology
MH  - Predictive Value of Tests
MH  - Risk Assessment/methods
MH  - Young Adult
PMC - PMC8851925
OTO - NOTNLM
OT  - GAD autoantibodies
OT  - HLA
OT  - prediction
OT  - type 1 diabetes
EDAT- 2021/11/09 06:00
MHDA- 2022/03/03 06:00
PMCR- 2021/11/08
CRDT- 2021/11/08 08:55
PHST- 2021/07/28 00:00 [received]
PHST- 2021/11/09 06:00 [pubmed]
PHST- 2022/03/03 06:00 [medline]
PHST- 2021/11/08 08:55 [entrez]
PHST- 2021/11/08 00:00 [pmc-release]
AID - 6423226 [pii]
AID - dgab816 [pii]
AID - 10.1210/clinem/dgab816 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2022 Feb 17;107(3):e935-e946. doi: 
      10.1210/clinem/dgab816.