PMID- 35903316
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220731
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 9
DP  - 2022
TI  - From Disease and Patient Heterogeneity to Precision Medicine in Type 1 Diabetes.
PG  - 932086
LID - 10.3389/fmed.2022.932086 [doi]
LID - 932086
AB  - Type 1 diabetes (T1D) remains a devastating disease that requires much effort to 
      control. Life-long daily insulin injections or an insulin pump are required to 
      avoid severe complications. With many factors contributing to disease onset, T1D 
      is a complex disease to cure. In this review, the risk factors, pathophysiology 
      and defect pathways are discussed. Results from (pre)clinical studies are 
      highlighted that explore restoration of insulin production and reduction of 
      autoimmunity. It has become clear that treatment responsiveness depends on 
      certain pathophysiological or genetic characteristics that differ between 
      patients. For instance, age at disease manifestation associated with efficacy of 
      immune intervention therapies, such as depleting islet-specific effector T cells 
      or memory B cells and increasing immune regulation. The new challenge is to 
      determine in whom to apply which intervention strategy. Within patients with high 
      rates of insulitis in early T1D onset, therapy depleting T cells or targeting B 
      lymphocytes may have a benefit, whereas slow progressing T1D in adults may be 
      better served with more sophisticated, precise and specific disease modifying 
      therapies. Genetic barcoding and immune profiling may help determining from which 
      new T1D endotypes patients suffer. Furthermore, progressed T1D needs 
      replenishment of insulin production besides autoimmunity reversal, as too many 
      beta cells are already lost or defect. Recurrent islet autoimmunity and allograft 
      rejection or necrosis seem to be the most challenging obstacles. Since beta cells 
      are highly immunogenic under stress, treatment might be more effective with 
      stress reducing agents such as glucagon-like peptide 1 (GLP-1) analogs. Moreover, 
      genetic editing by CRISPR-Cas9 allows to create hypoimmunogenic beta cells with 
      modified human leukocyte antigen (HLA) expression that secrete immune regulating 
      molecules. Given the differences in T1D between patients, stratification of 
      endotypes in clinical trials seems essential for precision medicines and clinical 
      decision making.
CI  - Copyright (c) 2022 Hollander and Roep.
FAU - den Hollander, Nicoline H M
AU  - den Hollander NHM
AD  - Department of Internal Medicine, Leiden University Medical Center, Leiden, 
      Netherlands.
AD  - Graduate School, Utrecht University, Utrecht, Netherlands.
FAU - Roep, Bart O
AU  - Roep BO
AD  - Department of Internal Medicine, Leiden University Medical Center, Leiden, 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220712
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC9314738
OTO - NOTNLM
OT  - autoimmune disease (AD)
OT  - disease endotypes
OT  - disease heterogeneity
OT  - genetic risk score
OT  - immune intervention therapy
OT  - islet autoimmunity
OT  - type 1 diabetes immunopathogenesis
COIS- The 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- 2022/07/30 06:00
MHDA- 2022/07/30 06:01
PMCR- 2022/07/12
CRDT- 2022/07/29 01:58
PHST- 2022/04/29 00:00 [received]
PHST- 2022/06/13 00:00 [accepted]
PHST- 2022/07/29 01:58 [entrez]
PHST- 2022/07/30 06:00 [pubmed]
PHST- 2022/07/30 06:01 [medline]
PHST- 2022/07/12 00:00 [pmc-release]
AID - 10.3389/fmed.2022.932086 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2022 Jul 12;9:932086. doi: 10.3389/fmed.2022.932086. 
      eCollection 2022.