PMID- 25231450
OWN - NLM
STAT- MEDLINE
DCOM- 20150527
LR  - 20220331
IS  - 1662-2979 (Electronic)
IS  - 1421-7082 (Linking)
VI  - 26
DP  - 2014
TI  - Thyroid autoimmunity.
PG  - 139-57
LID - 10.1159/000363161 [doi]
AB  - Autoimmune thyroid disease (AITD) is a multifactorial disease in which 
      autoimmunity against thyroid antigens develops against a particular genetic 
      background facilitated by exposure to environmental factors. Immunogenicity of 
      the major thyroid antigens thyroid peroxidase, thyroglobulin (TG) and thyrotropin 
      receptor (TSHR) is increased by genetic polymorphisms, a high number of antigenic 
      peptides available for binding to human leukocyte antigen (HLA), and a high 
      degree of glycosylation. Antigens bound to HLA are presented by 
      antigen-presenting cells to T cell receptors. Further interaction between both 
      cells is required via binding of CD40 ligand to CD40 and of B7-1/2 to CD28 for 
      activation of T cells. Complex regulatory mechanisms serve to prevent an immune 
      response directed against 'self'-antigens in the thymus (central tolerance) and 
      in peripheral tissues (peripheral tolerance) with the help of regulatory T cells. 
      Breakdown of tolerance to thyroid antigens can result in thyroid autoimmunity, 
      which may happen in subjects who have the wrong genes and who are exposed to the 
      wrong environment. Polymorphisms in thyroid genes (TG, TSHR) and immunoregulatory 
      genes (HLA, CTLA4, PTPN22, CD40, FCRL3, IL2RA, FOXP3) would contribute for about 
      70% to AITD, and environmental exposures (like iodine, smoking, infections, 
      parity) for the remaining 30%. Thyroid-infiltrating activated T cells may lead to 
      cell-mediated immunity, thyroid injury and eventually hypothyroidism, whereas 
      humoral immunity via TSHR-stimulating antibodies may give rise to 
      hyperthyroidism. Pediatric Hashimoto's and Graves' disease are less prevalent 
      than in adults, and the female preponderance is also less marked in children. The 
      discrepancy is probably due to relatively less involvement of environmental 
      insults in children, whereas the prevalence of risk alleles in AITD children is 
      higher than in AITD adults.
FAU - Wiersinga, Wilmar M
AU  - Wiersinga WM
AD  - Department of Endocrinology and Metabolism, Academic Medical Center, University 
      of Amsterdam, Amsterdam, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140829
PL  - Switzerland
TA  - Endocr Dev
JT  - Endocrine development
JID - 101138956
RN  - 0 (Receptors, Thyrotropin)
RN  - 9010-34-8 (Thyroglobulin)
RN  - EC 1.11.1.8 (Iodide Peroxidase)
SB  - IM
MH  - Autoimmune Diseases/genetics/*immunology
MH  - Humans
MH  - Iodide Peroxidase/*immunology
MH  - Receptors, Thyrotropin/*immunology
MH  - Thyroglobulin/*immunology
MH  - Thyroid Diseases/genetics/*immunology
EDAT- 2014/09/19 06:00
MHDA- 2015/05/28 06:00
CRDT- 2014/09/19 06:00
PHST- 2014/09/19 06:00 [entrez]
PHST- 2014/09/19 06:00 [pubmed]
PHST- 2015/05/28 06:00 [medline]
AID - 000363161 [pii]
AID - 10.1159/000363161 [doi]
PST - ppublish
SO  - Endocr Dev. 2014;26:139-57. doi: 10.1159/000363161. Epub 2014 Aug 29.