PMID- 33706238
OWN - NLM
STAT- MEDLINE
DCOM- 20220118
LR  - 20220503
IS  - 1095-9157 (Electronic)
IS  - 0896-8411 (Print)
IS  - 0896-8411 (Linking)
VI  - 119
DP  - 2021 May
TI  - HLA class I hyper-expression unmasks beta cells but not alpha cells to the immune 
      system in pre-diabetes.
PG  - 102628
LID - S0896-8411(21)00036-6 [pii]
LID - 10.1016/j.jaut.2021.102628 [doi]
AB  - Human leukocyte antigens of class-I (HLA-I) molecules are hyper-expressed in 
      insulin-containing islets (ICI) of type 1 diabetic (T1D) donors. This study 
      investigated the HLA-I expression in autoantibody positive (AAB+) donors and 
      defined its intra-islet and intracellular localization as well as proximity to 
      infiltrating CD8 T cells with high-resolution confocal microscopy. We found HLA-I 
      hyper-expression had already occurred prior to clinical diagnosis of T1D in 
      islets of AAB+ donors. Interestingly, throughout all stages of disease, HLA-I was 
      mostly expressed by alpha cells. Hyper-expression in AAB+ and T1D donors was 
      associated with intra-cellular accumulation in the Golgi. Proximity analysis 
      showed a moderate but significant correlation between HLA-I and infiltrating CD8 
      T cells only in ICI of T1D donors, but not in AAB+ donors. These observations not 
      only demonstrate a very early, islet-intrinsic immune-independent increase of 
      HLA-I during diabetes pathogenesis, but also point towards a role for alpha cells 
      in T1D.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Benkahla, Mehdi A
AU  - Benkahla MA
AD  - La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, 92037, CA, USA.
FAU - Sabouri, Somayeh
AU  - Sabouri S
AD  - La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, 92037, CA, USA.
FAU - Kiosses, William B
AU  - Kiosses WB
AD  - La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, 92037, CA, USA.
FAU - Rajendran, Sakthi
AU  - Rajendran S
AD  - La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, 92037, CA, USA.
FAU - Quesada-Masachs, Estefania
AU  - Quesada-Masachs E
AD  - La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, 92037, CA, USA.
FAU - von Herrath, Matthias G
AU  - von Herrath MG
AD  - La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, 92037, CA, USA; 
      Global Chief Medical Officer, Novo Nordisk, Denmark. Electronic address: 
      Matthias@lji.org.
LA  - eng
GR  - R01 AI092453/AI/NIAID NIH HHS/United States
GR  - R01 AI134971/AI/NIAID NIH HHS/United States
GR  - T32 DK007494/DK/NIDDK NIH HHS/United States
GR  - U01 AI102370/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210309
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Biomarkers)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Autoantibodies/immunology
MH  - Autoantigens/immunology
MH  - Autoimmunity
MH  - Biomarkers
MH  - Diabetes Mellitus, Type 1/etiology/metabolism
MH  - Disease Susceptibility/immunology
MH  - Fluorescent Antibody Technique
MH  - *Gene Expression
MH  - Glucagon-Secreting Cells/*metabolism
MH  - Histocompatibility Antigens Class I/*genetics/*immunology
MH  - Humans
MH  - Insulin-Secreting Cells/*immunology/*metabolism
MH  - Islets of Langerhans/immunology/metabolism/pathology
MH  - Prediabetic State/*etiology/*immunology
MH  - Protein Transport
MH  - T-Lymphocyte Subsets/immunology/metabolism
PMC - PMC8044030
MID - NIHMS1681590
OTO - NOTNLM
OT  - Alpha cells
OT  - Beta cells
OT  - HLA class I
OT  - Type 1 diabetes
OT  - nPOD
COIS- Competing interests: The authors declare no competing interest.
EDAT- 2021/03/12 06:00
MHDA- 2022/01/19 06:00
PMCR- 2022/05/01
CRDT- 2021/03/11 20:34
PHST- 2020/12/10 00:00 [received]
PHST- 2021/02/17 00:00 [revised]
PHST- 2021/02/25 00:00 [accepted]
PHST- 2021/03/12 06:00 [pubmed]
PHST- 2022/01/19 06:00 [medline]
PHST- 2021/03/11 20:34 [entrez]
PHST- 2022/05/01 00:00 [pmc-release]
AID - S0896-8411(21)00036-6 [pii]
AID - 10.1016/j.jaut.2021.102628 [doi]
PST - ppublish
SO  - J Autoimmun. 2021 May;119:102628. doi: 10.1016/j.jaut.2021.102628. Epub 2021 Mar 
      9.