PMID- 37580967
OWN - NLM
STAT- MEDLINE
DCOM- 20231011
LR  - 20231011
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 25
IP  - 11
DP  - 2023 Nov
TI  - A 1-year pilot study of intralymphatic injections of GAD-alum in individuals with 
      latent autoimmune diabetes in adults (LADA) with signs of high immunity: No 
      safety concerns and resemblance to juvenile type 1 diabetes.
PG  - 3400-3409
LID - 10.1111/dom.15239 [doi]
AB  - AIMS: To test, for the first time in latent autoimmune diabetes in adults (LADA), 
      the effects of autoantigen-specific immunotherapy by intralymphatic 
      administration of aluminium-formulated recombinant human glutamic acid 
      decarboxylase 65 (GAD-alum); specifically, to test if this treatment is safe, to 
      test whether it induces a strong immunological response akin to a similar 
      protocol in type 1 diabetes and to look for associations with preserved beta-cell 
      function. MATERIALS AND METHODS: Three GAD-alum injections, 4 mug each, were 
      administered 1 month apart into an inguinal lymph node in 14 people with newly 
      diagnosed LADA (age 30-62 years) presenting with high levels of antibodies 
      against glutamic acid decarboxylase (GADA). Adverse effects, immunological 
      variables and beta-cell function were monitored, with detailed measurements at 5 
      and 12 months from baseline. RESULTS: Clinical adverse effects were minor and 
      transient and measured laboratory variables were unaffected. All participants 
      completed the study. Treatment raised levels of GADA, elicited strong effects on 
      reactivity of peripheral blood mononuclear cells to GAD and raised 
      cytokine/chemokine levels. Beta-cell function appeared stable preferentially in 
      the seven participants carrying human leukocyte antigen (HLA) haplotypes DR3DQ2, 
      as assessed by C-peptide glucagon tests (P < 0.05 vs. seven non-carriers). 
      CONCLUSION: Intralymphatic treatment with GAD-alum in LADA is without clinical or 
      other safety concerns over a 12-month period. As in a similar protocol used in 
      type 1 diabetes, treatment exerts a strong immunological impact and is compatible 
      with protection of beta-cell function preferentially in HLA-DR3DQ2 LADA patients. 
      These findings pave the way for a randomized controlled trial in this important 
      subgroup of LADA patients.
CI  - (c) 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & 
      Sons Ltd.
FAU - Hals, Ingrid K
AU  - Hals IK
AUID- ORCID: 0000-0003-3753-0913
AD  - Department of Clinical and Molecular Medicine, Norwegian University of Science 
      and Technology (NTNU), Trondheim, Norway.
AD  - Department of Endocrinology, Clinic of Medicine, St Olavs Hospital, Trondheim 
      University Hospital, Trondheim, Norway.
AD  - Department of Research, Nord-Trondelag Hospital Trust, Levanger, Norway.
FAU - Balasuriya, Chandima
AU  - Balasuriya C
AUID- ORCID: 0000-0002-2252-8741
AD  - Department of Endocrinology, Clinic of Medicine, St Olavs Hospital, Trondheim 
      University Hospital, Trondheim, Norway.
FAU - Casas, Rosaura
AU  - Casas R
AUID- ORCID: 0000-0002-7414-6104
AD  - Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty 
      of Medicine and Health Sciences, Linkoping University, Linkoping, Sweden.
FAU - Ludvigsson, Johnny
AU  - Ludvigsson J
AUID- ORCID: 0000-0003-1695-5234
AD  - Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty 
      of Medicine and Health Sciences, Linkoping University, Linkoping, Sweden.
AD  - Crown Princess Victoria Children's Hospital, Linkoping, Sweden.
FAU - Bjorklund, Anneli
AU  - Bjorklund A
AUID- ORCID: 0000-0001-8616-6826
AD  - Department of Molecular medicine and Surgery, Karolinska Institutet, Stockholm, 
      Sweden.
AD  - Center for Diabetes, Academic Specialist Center, Stockholm, Sweden.
FAU - Grill, Valdemar
AU  - Grill V
AUID- ORCID: 0000-0001-6959-022X
AD  - Department of Clinical and Molecular Medicine, Norwegian University of Science 
      and Technology (NTNU), Trondheim, Norway.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230814
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 34S289N54E (aluminum sulfate)
RN  - 0 (Autoantibodies)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Middle Aged
MH  - Autoantibodies
MH  - *Diabetes Mellitus, Type 1/therapy
MH  - *Glucose Intolerance/drug therapy
MH  - *Glutamate Decarboxylase/adverse effects/therapeutic use
MH  - Injections, Intralymphatic
MH  - *Latent Autoimmune Diabetes in Adults/drug therapy
MH  - Leukocytes, Mononuclear
MH  - Pilot Projects
OTO - NOTNLM
OT  - beta-cell function
OT  - clinical trial
OT  - drug development
OT  - insulin secretion
OT  - phase I-II study
OT  - type 1 diabetes
EDAT- 2023/08/15 06:42
MHDA- 2023/10/04 06:43
CRDT- 2023/08/15 03:09
PHST- 2023/07/13 00:00 [revised]
PHST- 2023/04/23 00:00 [received]
PHST- 2023/07/22 00:00 [accepted]
PHST- 2023/10/04 06:43 [medline]
PHST- 2023/08/15 06:42 [pubmed]
PHST- 2023/08/15 03:09 [entrez]
AID - 10.1111/dom.15239 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2023 Nov;25(11):3400-3409. doi: 10.1111/dom.15239. Epub 2023 
      Aug 14.