PMID- 37509587
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230731
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 11
IP  - 7
DP  - 2023 Jul 10
TI  - GABA and Combined GABA with GAD65-Alum Treatment Alters Th1 Cytokine Responses of 
      PBMCs from Children with Recent-Onset Type 1 Diabetes.
LID - 10.3390/biomedicines11071948 [doi]
LID - 1948
AB  - Type 1 diabetes (T1D) is an autoimmune disease culminating in the destruction of 
      insulin-producing pancreatic cells. There is a need for the development of novel 
      antigen-specific strategies to delay cell destruction, including combinatorial 
      strategies that do not elicit systemic immunosuppression. Gamma-aminobutyric acid 
      (GABA) is expressed by immune cells, beta-cells, and gut bacteria and is 
      immunomodulatory. Glutamic-acid decarboxylase 65 (GAD65), which catalyzes GABA 
      from glutamate, is a T1D autoantigen. To test the efficacy of combinatorial GABA 
      treatment with or without GAD65-immunization to dampen autoimmune responses, we 
      enrolled recent-onset children with T1D in a one-year clinical trial 
      (ClinicalTrials.gov NCT02002130) and examined T cell responses. We isolated 
      peripheral blood mononuclear cells and evaluated cytokine responses following 
      polyclonal activation and GAD65 rechallenge. Both GABA alone and GABA/GAD65-alum 
      treatment inhibited Th1 cytokine responses over the 12-month study with both 
      polyclonal and GAD65 restimulation. We also investigated whether patients with 
      HLA-DR3-DQ2 and HLA-DR4-DQ8, the two highest-risk human leukocyte antigen (HLA) 
      haplotypes in T1D, exhibited differences in response to GABA alone and 
      GABA/GAD65-alum. HLA-DR4-DQ8 patients possessed a Th1-skewed response compared to 
      HLA-DR3-DQ2 patients. We show that GABA and GABA/GAD65-alum present an attractive 
      immunomodulatory treatment for children with T1D and that HLA haplotypes should 
      be considered.
FAU - Heath, Katie E
AU  - Heath KE
AD  - Department of Microbiology, Comprehensive Diabetes Center, University of Alabama 
      at Birmingham, Birmingham, AL 35294, USA.
FAU - Feduska, Joseph M
AU  - Feduska JM
AUID- ORCID: 0000-0002-5688-5819
AD  - Department of Microbiology, Comprehensive Diabetes Center, University of Alabama 
      at Birmingham, Birmingham, AL 35294, USA.
FAU - Taylor, Jared P
AU  - Taylor JP
AUID- ORCID: 0000-0001-7700-530X
AD  - Department of Microbiology, Comprehensive Diabetes Center, University of Alabama 
      at Birmingham, Birmingham, AL 35294, USA.
FAU - Houp, Julie A
AU  - Houp JA
AD  - Department of Surgery, Heersink School of Medicine, University of Alabama at 
      Birmingham, Birmingham, AL 35294, USA.
FAU - Botta, Davide
AU  - Botta D
AUID- ORCID: 0000-0003-3926-0662
AD  - Department of Microbiology, Comprehensive Diabetes Center, University of Alabama 
      at Birmingham, Birmingham, AL 35294, USA.
FAU - Lund, Frances E
AU  - Lund FE
AUID- ORCID: 0000-0003-3083-1246
AD  - Department of Microbiology, Comprehensive Diabetes Center, University of Alabama 
      at Birmingham, Birmingham, AL 35294, USA.
FAU - Mick, Gail J
AU  - Mick GJ
AD  - Department of Pediatrics, Division of Pediatric Endocrinology, University of 
      Alabama at Birmingham, Birmingham, AL 35294, USA.
FAU - McGwin, Gerald Jr
AU  - McGwin G Jr
AD  - Department of Epidemiology, School of Public Health, University of Alabama at 
      Birmingham, Birmingham, AL 35294, USA.
FAU - McCormick, Kenneth L
AU  - McCormick KL
AD  - Department of Pediatrics, Division of Pediatric Endocrinology, University of 
      Alabama at Birmingham, Birmingham, AL 35294, USA.
FAU - Tse, Hubert M
AU  - Tse HM
AD  - Department of Microbiology, Molecular Genetics, and Immunology, University of 
      Kansas Medical Center, Mail Stop 3029, 1012 Wahl Hall West, 3901 Rainbow 
      Boulevard, Kansas City, KS 66160, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02002130
GR  - 201303440/JDRF/Juvenile Diabetes Research Foundation/United States
PT  - Journal Article
DEP - 20230710
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC10377053
OTO - NOTNLM
OT  - GABA
OT  - GAD65
OT  - autoimmunity
OT  - cytokine
OT  - type 1 diabetes
COIS- All authors have no conflict of interest relevant to this article.
EDAT- 2023/07/29 11:48
MHDA- 2023/07/29 11:49
PMCR- 2023/07/10
CRDT- 2023/07/29 01:13
PHST- 2023/05/19 00:00 [received]
PHST- 2023/06/19 00:00 [revised]
PHST- 2023/06/29 00:00 [accepted]
PHST- 2023/07/29 11:49 [medline]
PHST- 2023/07/29 11:48 [pubmed]
PHST- 2023/07/29 01:13 [entrez]
PHST- 2023/07/10 00:00 [pmc-release]
AID - biomedicines11071948 [pii]
AID - biomedicines-11-01948 [pii]
AID - 10.3390/biomedicines11071948 [doi]
PST - epublish
SO  - Biomedicines. 2023 Jul 10;11(7):1948. doi: 10.3390/biomedicines11071948.