PMID- 34850014
OWN - NLM
STAT- MEDLINE
DCOM- 20220415
LR  - 20221128
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 107
IP  - 4
DP  - 2022 Mar 24
TI  - Association of High-Affinity Autoantibodies With Type 1 Diabetes High-Risk HLA 
      Haplotypes.
PG  - e1510-e1517
LID - 10.1210/clinem/dgab853 [doi]
AB  - OBJECTIVE: Electrochemiluminescence (ECL) assays are high-affinity autoantibody 
      (Ab) tests that are more specific than Abs detected by traditional radiobinding 
      assays (RBA) for risk screening and prediction of progression to type 1 diabetes. 
      We sought to characterize the association of high-risk human leukocyte antigen 
      (HLA) haplotypes and genotypes with ECL positivity and levels in relatives of 
      individuals with type 1 diabetes. METHODS: We analyzed 602 participants from the 
      TrialNet Pathway to Prevention Study who were positive for at least 1 RBA 
      diabetes-related Ab [glutamic acid decarboxylase autoantibodies (GADA) or insulin 
      autoantibodies (IAA)] and for whom ECL and HLA data were available. ECL and RBA 
      Ab levels were converted to SD units away from mean (z-scores) for analyses. 
      RESULTS: Mean age at initial visit was 19.4 +/- 13.7 years; 344 (57.1%) were female 
      and 104 (17.3%) carried the high-risk HLA-DR3/4*0302 genotype. At initial visit 
      424/602 (70.4%) participants were positive for either ECL-GADA or ECL-IAA, and 
      178/602 (29.6%) were ECL negative. ECL and RBA-GADA positivity were associated 
      with both HLA-DR3 and DR4 haplotypes (all Ps < 0.05), while ECL and RBA-GADA 
      z-score titers were higher in participants with HLA-DR3 haplotypes only (both Ps 
      < 0.001). ECL-IAA (but not RBA-IAA) positivity was associated with the HLA-DR4 
      haplotype (P < 0.05). CONCLUSIONS: ECL-GADA positivity is associated with the 
      HLA-DR3 and HLA-DR4 haplotypes and levels are associated with the HLA-DR3 
      haplotype. ECL-IAA positivity is associated with HLA-DR4 haplotype. These studies 
      further contribute to the understanding of genetic risk and islet autoimmunity 
      endotypes in type 1 diabetes.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Triolo, Taylor M
AU  - Triolo TM
AUID- ORCID: 0000-0003-4796-6542
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 
      USA.
FAU - Pyle, Laura
AU  - Pyle L
AUID- ORCID: 0000-0001-5577-8221
AD  - Department of Pediatrics, University of Colorado, Aurora, CO, USA.
AD  - Department of Biostatistics and Informatics, Colorado School of Public Health, 
      Aurora, CO, USA.
FAU - Broncucia, Hali
AU  - Broncucia H
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 
      USA.
FAU - Armstrong, Taylor
AU  - Armstrong T
AUID- ORCID: 0000-0003-4931-2331
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 
      USA.
FAU - Yu, Liping
AU  - Yu L
AUID- ORCID: 0000-0003-0664-2154
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 
      USA.
FAU - Gottlieb, Peter A
AU  - Gottlieb PA
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 
      USA.
FAU - Steck, Andrea K
AU  - Steck AK
AUID- ORCID: 0000-0002-5931-9484
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, 
      USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00097292
GR  - U01 DK085476/DK/NIDDK NIH HHS/United States
GR  - K12DK094712/DK/NIDDK NIH HHS/United States
GR  - U01 DK061010/DK/NIDDK NIH HHS/United States
GR  - JDRF/Juvenile Diabetes Research Foundation/United States
GR  - U01 DK085499/DK/NIDDK NIH HHS/United States
GR  - U01 DK085463/DK/NIDDK NIH HHS/United States
GR  - U01 DK103266/DK/NIDDK NIH HHS/United States
GR  - AI/NIAID NIH HHS/United States
GR  - U01 DK085466/DK/NIDDK NIH HHS/United States
GR  - U01 DK103153/DK/NIDDK NIH HHS/United States
GR  - U01 DK061058/DK/NIDDK NIH HHS/United States
GR  - U01 DK085505/DK/NIDDK NIH HHS/United States
GR  - U01 DK085453/DK/NIDDK NIH HHS/United States
GR  - U01 DK061042/DK/NIDDK NIH HHS/United States
GR  - U01 DK061034/DK/NIDDK NIH HHS/United States
GR  - U01 DK085461/DK/NIDDK NIH HHS/United States
GR  - U01 DK085509/DK/NIDDK NIH HHS/United States
GR  - K12 DK094712/DK/NIDDK NIH HHS/United States
GR  - U01 DK103180/DK/NIDDK NIH HHS/United States
GR  - U01 DK085465/DK/NIDDK NIH HHS/United States
GR  - U01 DK085504/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
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 (HLA Antigens)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (HLA-DR4 Antigen)
RN  - 0 (Insulin Antibodies)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Autoantibodies
MH  - Child
MH  - Child, Preschool
MH  - *Diabetes Mellitus, Type 1/diagnosis
MH  - Female
MH  - Glutamate Decarboxylase
MH  - HLA Antigens/genetics
MH  - HLA-DR3 Antigen/genetics
MH  - HLA-DR4 Antigen/genetics
MH  - Haplotypes
MH  - Humans
MH  - Insulin Antibodies
MH  - Male
MH  - Young Adult
PMC - PMC8947772
OTO - NOTNLM
OT  - HLA genotyping
OT  - autoantibody
OT  - electrochemiluminescence assay
OT  - epidemiology
OT  - genetics
OT  - prediction
OT  - type 1 diabetes
EDAT- 2021/12/02 06:00
MHDA- 2022/04/16 06:00
PMCR- 2022/11/27
CRDT- 2021/12/01 07:20
PHST- 2021/08/02 00:00 [received]
PHST- 2021/12/02 06:00 [pubmed]
PHST- 2022/04/16 06:00 [medline]
PHST- 2021/12/01 07:20 [entrez]
PHST- 2022/11/27 00:00 [pmc-release]
AID - 6444375 [pii]
AID - dgab853 [pii]
AID - 10.1210/clinem/dgab853 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1510-e1517. doi: 
      10.1210/clinem/dgab853.