PMID- 37026004
OWN - NLM
STAT- MEDLINE
DCOM- 20230410
LR  - 20230702
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Matching for HLA-DR excluding diabetogenic HLA-DR3 and HLA-DR4 predicts insulin 
      independence after pancreatic islet transplantation.
PG  - 1110544
LID - 10.3389/fimmu.2023.1110544 [doi]
LID - 1110544
AB  - INTRODUCTION: In pancreatic islet transplantation, the exact contribution of 
      human leukocyte antigen (HLA) matching to graft survival remains unclear. Islets 
      may be exposed to allogenic rejection but also the recurrence of type 1 diabetes 
      (T1D). We evaluated the HLA-DR matching, including the impact of diabetogenic 
      HLA-DR3 or HLA-DR4 matches. METHODS: We retrospectively examined the HLA profile 
      in 965 transplant recipients and 2327 islet donors. The study population was 
      obtained from patients enrolled in the Collaborative Islet Transplant Registry. 
      We then identified 87 recipients who received a single-islet infusion. 
      Islet-kidney recipients, 2nd islet infusion, and patients with missing data were 
      excluded from the analysis (n=878). RESULTS: HLA-DR3 and HLA-DR4 were present in 
      29.7% and 32.6% of T1D recipients and 11.6% and 15.8% of the donors, 
      respectively. We identified 52 T1D islet recipients mismatched for HLA-DR (group 
      A), 11 with 1 or 2 HLA-DR-matches but excluding HLA-DR3 and HLA- DR4 (group B), 
      and 24 matched for HLA-DR3 or HLA-DR4 (group C). Insulin-independence was 
      maintained in a significantly higher percentage of group B recipients from year 
      one through five post-transplantation (p<0.01). At five-year 
      post-transplantation, 78% of group B was insulin-independent compared to 24% 
      (group A) and 35% (group C). Insulin-independence correlated with significantly 
      better glycemic control (HbA1c <7%), fasting blood glucose, and reduced severe 
      hypoglycemic events. Matching HLA-A-B-DR (>/=3) independently of HLA- DR3 or 
      HLA-DR4 matching did not improve graft survival. CONCLUSION: This study suggests 
      that matching HLA-DR but excluding the diabetogenic HLA-DR3 and/or 4 is a 
      significant predictor for long-term islet survival.
CI  - Copyright (c) 2023 Ballou, Barton, Payne, Berney, Villard, Meier, Baidal, 
      Alejandro, Robien, Eggerman, Kamoun and Muller.
FAU - Ballou, Cassandra
AU  - Ballou C
AD  - Collaborative Islet Transplant Registry Coordinating Center, The EMMES Company, 
      LLC, Rockville, MD, United States.
FAU - Barton, Franca
AU  - Barton F
AD  - Collaborative Islet Transplant Registry Coordinating Center, The EMMES Company, 
      LLC, Rockville, MD, United States.
FAU - Payne, Elizabeth H
AU  - Payne EH
AD  - Collaborative Islet Transplant Registry Coordinating Center, The EMMES Company, 
      LLC, Rockville, MD, United States.
FAU - Berney, Thierry
AU  - Berney T
AD  - Division of Transplantation, Department of Surgery, Geneva University Hospitals, 
      Geneva, Switzerland.
FAU - Villard, Jean
AU  - Villard J
AD  - Department of Genetic, Laboratory and Pathology Medicine, Geneva University 
      Hospitals, Geneva, Switzerland.
FAU - Meier, Raphael P H
AU  - Meier RPH
AD  - Department of Surgery, School of Medicine, University of Maryland, Baltimore, MD, 
      United States.
FAU - Baidal, David
AU  - Baidal D
AD  - Department of Medicine and the Diabetes Research Institute, University of Miami 
      Miller School of Medicine, Miami, FL, United States.
FAU - Alejandro, Rodolfo
AU  - Alejandro R
AD  - Department of Medicine and the Diabetes Research Institute, University of Miami 
      Miller School of Medicine, Miami, FL, United States.
FAU - Robien, Mark
AU  - Robien M
AD  - National Institute of Allergy and Infectious Diseases, National Institutes of 
      Health, Bethesda, MD, United States.
FAU - Eggerman, Thomas L
AU  - Eggerman TL
AD  - National Institute of Diabetes and Digestive and Kidney Diseases, National 
      Institutes of Health, Bethesda, MD, United States.
FAU - Kamoun, Malek
AU  - Kamoun M
AD  - Immunology and Histocompatibility Testing Laboratory, University of Pennsylvania 
      Perelman School of Medicine, Philadelphia, PA, United States.
FAU - Muller, Yannick D
AU  - Muller YD
AD  - Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois and 
      University of Lausanne, Lausanne, Switzerland.
LA  - eng
GR  - I50 HX001229/HX/HSRD VA/United States
GR  - K23 DK099440/DK/NIDDK NIH HHS/United States
GR  - U01 DK133709/DK/NIDDK NIH HHS/United States
GR  - UC4 DK114839/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230321
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (HLA-DR4 Antigen)
RN  - 0 (Insulin)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 1
MH  - HLA-DR3 Antigen
MH  - HLA-DR4 Antigen/analysis
MH  - Insulin
MH  - *Islets of Langerhans Transplantation
MH  - Retrospective Studies
MH  - *Histocompatibility Testing
PMC - PMC10070978
OTO - NOTNLM
OT  - HLA
OT  - HLA-DR3
OT  - HLA-DR4
OT  - Human leukocyte antigen
OT  - insulin
OT  - insulin independence
OT  - islet transplantation
OT  - type 1 diabetes
COIS- Authors CB, FB and EP were employed by The EMMES Company, LLC. The remaining 
      authors declare that the research was conducted in the absence of any commercial 
      or financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2023/04/08 06:00
MHDA- 2023/04/10 06:42
PMCR- 2023/01/01
CRDT- 2023/04/07 02:37
PHST- 2022/11/28 00:00 [received]
PHST- 2023/02/16 00:00 [accepted]
PHST- 2023/04/10 06:42 [medline]
PHST- 2023/04/07 02:37 [entrez]
PHST- 2023/04/08 06:00 [pubmed]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1110544 [doi]
PST - epublish
SO  - Front Immunol. 2023 Mar 21;14:1110544. doi: 10.3389/fimmu.2023.1110544. 
      eCollection 2023.