KEGG   PATHWAY: uah05320
Entry
uah05320                    Pathway                                
Name
Autoimmune thyroid disease - Ursus arctos (brown bear)
Description
The classification of autoimmune throid disease (AITD) includes Hashimoto's thyroiditis (HT) or chronic autoimmune thyroiditis and its variants, Graves' disease (GD) and autoimmune atrophic thyroiditis or primary myxedema. HT is characterized by the presence of goitre, thyroid autoantibodies against thyroid peroxidase (TPO) and thyroglobulin (Tg) in serum and varying degrees of thyroid dysfunction. During HT, self-reactive CD4+ T lymphocytes (Th) recruit B cells and CD8+ T cells (CTL) into the thyroid. Disease progression leads to the death of thyroid cells and hypothyroidism. Both autoantibodies and thyroid-specific cytotoxic T lymphocytes (CTLs) have been proposed to be responsible for autoimmune thyrocyte depletion. In GD, the TSH-R is the most important autoantigen. Antibodies directed against it mimic the effects of the hormone on thyroid cells, TSH, stimulating autonomous production of thyroxine and triiodothyronine and causing hyperthyroidism. The presence of TSH-R-blocking antibodies that bind the TSH receptor in a similar fashion to the antibodies in patients with Grave's disease but that block rather than activate the receptor explains some cases of atrophic hypothyroidism.
Class
Human Diseases; Immune disease
Pathway map
uah05320  Autoimmune thyroid disease
uah05320

Organism
Ursus arctos (brown bear) [GN:uah]
Gene
113241871  CD40LG; CD40 ligand [KO:K03161]
113242596  IL10; interleukin-10 [KO:K05443]
113243684  [KO:K06752]
113243685  [KO:K06752]
113243706  [KO:K06751]
113243774  [KO:K06752]
113243775  [KO:K06752]
113243776  [KO:K06752]
113243777  [KO:K06752]
113243778  [KO:K06752]
113243779  [KO:K06752]
113243784  [KO:K06752]
113243786  [KO:K06752]
113243788  [KO:K06752]
113243878  [KO:K06751]
113244442  TSHB; thyrotropin subunit beta [KO:K05251]
113245994  [KO:K01353] [EC:3.4.21.79]
113250163  [KO:K06751]
113250557  CTLA4; cytotoxic T-lymphocyte protein 4 [KO:K06538]
113250560  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
113251861  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
113252170  CD86; T-lymphocyte activation antigen CD86 isoform X6 [KO:K05413]
113252704  TG; thyroglobulin [KO:K10809]
113255635  IL2; interleukin-2 [KO:K05429]
113258674  CD40; tumor necrosis factor receptor superfamily member 5 isoform X2 [KO:K03160]
113258968  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
113259145  PRF1; perforin-1 [KO:K07818]
113260290  [KO:K05414]
113260291  [KO:K05414]
113260293  [KO:K05414]
113260294  [KO:K05414]
113261534  [KO:K06751]
113261714  IL5; interleukin-5 [KO:K05428]
113261716  IL4; interleukin-4 [KO:K05430]
113262825  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
113264851  CGA; glycoprotein hormones alpha chain [KO:K08522]
113269244  TPO; LOW QUALITY PROTEIN: thyroid peroxidase [KO:K00431] [EC:1.11.1.8]
113270272  TSHR; thyrotropin receptor isoform X1 [KO:K04249]
123000236  [KO:K06751]
125283239  [KO:K05414]
125283240  [KO:K05414]
125283241  [KO:K05414]
125283243  [KO:K05414]
125283244  [KO:K05414]
125283245  [KO:K05414]
125283246  [KO:K05414]
125283247  [KO:K05414]
125283248  [KO:K05414]
125283564  [KO:K06751]
Compound
C01382  Iodine
C01829  Thyroxine
C02465  Triiodothyronine
D00636  Amiodarone hydrochloride (JP18/USP)
Reference
  Authors
Fountoulakis S, Tsatsoulis A.
  Title
On the pathogenesis of autoimmune thyroid disease: a unifying hypothesis.
  Journal
Clin Endocrinol (Oxf) 60:397-409 (2004)
DOI:10.1046/j.1365-2265.2004.01978.x
Reference
  Authors
Chistiakov DA.
  Title
Immunogenetics of Hashimoto's thyroiditis.
  Journal
J Autoimmune Dis 2:1 (2005)
DOI:10.1186/1740-2557-2-1
Reference
PMID:9534029
  Authors
McIver B, Morris JC.
  Title
The pathogenesis of Graves' disease.
  Journal
Endocrinol Metab Clin North Am 27:73-89 (1998)
DOI:10.1016/S0889-8529(05)70299-1
Reference
  Authors
Stassi G, De Maria R.
  Title
Autoimmune thyroid disease: new models of cell death in autoimmunity.
  Journal
Nat Rev Immunol 2:195-204 (2002)
DOI:10.1038/nri750
Reference
  Authors
Collins J, Gough S.
  Title
Autoimmunity in thyroid disease.
  Journal
Eur J Nucl Med Mol Imaging 29 Suppl 2:S417-24 (2002)
DOI:10.1007/s00259-002-0848-8
Reference
  Authors
Ruwhof C, Drexhage HA.
  Title
Iodine and thyroid autoimmune disease in animal models.
  Journal
Thyroid 11:427-36 (2001)
DOI:10.1089/105072501300176381
Reference
  Authors
Tsatsoulis A.
  Title
The role of stress in the clinical expression of thyroid autoimmunity.
  Journal
Ann N Y Acad Sci 1088:382-95 (2006)
DOI:10.1196/annals.1366.015
Reference
  Authors
Prummel MF, Strieder T, Wiersinga WM.
  Title
The environment and autoimmune thyroid diseases.
  Journal
Eur J Endocrinol 150:605-18 (2004)
DOI:10.1530/eje.0.1500605
Reference
  Authors
Kopp P.
  Title
The TSH receptor and its role in thyroid disease.
  Journal
Cell Mol Life Sci 58:1301-22 (2001)
DOI:10.1007/PL00000941
Related
pathway
uah04210  Apoptosis
uah04514  Cell adhesion molecules
uah04610  Complement and coagulation cascades
uah04612  Antigen processing and presentation
uah04660  T cell receptor signaling pathway
uah04662  B cell receptor signaling pathway
uah04918  Thyroid hormone synthesis
KO pathway
ko05320   

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