PMID- 24752371
OWN - NLM
STAT- MEDLINE
DCOM- 20150519
LR  - 20220409
IS  - 1559-0267 (Electronic)
IS  - 1080-0549 (Linking)
VI  - 47
IP  - 2
DP  - 2014 Oct
TI  - Molecular mechanisms in autoimmune type 1 diabetes: a critical review.
PG  - 174-92
LID - 10.1007/s12016-014-8422-2 [doi]
AB  - Autoimmune type 1 diabetes is characterized by selective destruction of 
      insulin-secreting beta cells in the pancreas of genetically susceptible 
      individuals. The mechanisms underlying the development of type 1 diabetes are not 
      fully understood. However, a widely accepted point is that type 1 diabetes is 
      caused by a combination of genetic and environmental factors. Although most type 
      1 diabetes patients do not have a family history, genetic susceptibility does 
      play a vital role in beta cell autoimmunity and destruction. Human leukocyte 
      antigen (HLA) regions are the strongest genetic determinants, which can 
      contribute 40-50 % of the genetic risk to type 1 diabetes. Other genes, including 
      INS also contribute to disease risk. The mechanisms of the susceptible genes in 
      type 1 diabetes may relate to their respective roles in antigen presentation, 
      beta cell autoimmunity, immune tolerance, and autoreactive T cell response. 
      Environmental susceptibility factors also contribute to the risk of developing 
      type 1 diabetes. From an epigenetic standpoint, the pathologic mechanisms 
      involved in the development of type 1 diabetes may include DNA methylation, 
      histone modification, microRNA, and molecular mimicry. These mechanisms may act 
      through regulating of gene expression, thereby affecting the immune system 
      response toward islet beta cells. One of the characteristics of type 1 diabetes 
      is the recognition of islet autoantigens by autoreactive CD4(+) and CD8(+) T 
      cells and autoantibodies. Autoantibodies against islet autoantigens are involved 
      in autoantigen processing and presentation by HLA molecules. This review will 
      mainly focus on the molecular mechanism by which genetic, epigenetic, and 
      environmental factors contribute to the risk of type 1 diabetes.
FAU - Xie, Zhiguo
AU  - Xie Z
AD  - Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and 
      Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, 
      Central South University, Changsha, Hunan, 410011, China.
FAU - Chang, Christopher
AU  - Chang C
FAU - Zhou, Zhiguang
AU  - Zhou Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Clin Rev Allergy Immunol
JT  - Clinical reviews in allergy & immunology
JID - 9504368
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (HLA Antigens)
SB  - IM
EIN - Clin Rev Allergy Immunol. 2014 Oct;47(2):258
MH  - Antigen Presentation
MH  - Autoantibodies/biosynthesis
MH  - Autoantigens/genetics/immunology
MH  - *Autoimmunity
MH  - CD4-Positive T-Lymphocytes/immunology/pathology
MH  - CD8-Positive T-Lymphocytes/immunology/pathology
MH  - Diabetes Mellitus, Type 1/genetics/*immunology/pathology
MH  - Epigenesis, Genetic/*immunology
MH  - Gene-Environment Interaction
MH  - *Genetic Predisposition to Disease
MH  - HLA Antigens/genetics/immunology
MH  - Humans
MH  - Immune Tolerance
MH  - Insulin-Secreting Cells/*immunology/pathology
MH  - Molecular Mimicry
EDAT- 2014/04/23 06:00
MHDA- 2015/05/20 06:00
CRDT- 2014/04/23 06:00
PHST- 2014/04/23 06:00 [entrez]
PHST- 2014/04/23 06:00 [pubmed]
PHST- 2015/05/20 06:00 [medline]
AID - 10.1007/s12016-014-8422-2 [doi]
PST - ppublish
SO  - Clin Rev Allergy Immunol. 2014 Oct;47(2):174-92. doi: 10.1007/s12016-014-8422-2.