KEGG   PATHWAY: hsa05320
Entry
hsa05320                    Pathway                                
Name
Autoimmune thyroid disease - Homo sapiens (human)
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
hsa05320  Autoimmune thyroid disease
hsa05320

Drug
D00562  Propylthiouracil (JP18/USP/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
3439  IFNA1; interferon alpha 1 [KO:K05414]
3440  IFNA2; interferon alpha 2 [KO:K05414]
3441  IFNA4; interferon alpha 4 [KO:K05414]
3442  IFNA5; interferon alpha 5 [KO:K05414]
3443  IFNA6; interferon alpha 6 [KO:K05414]
3444  IFNA7; interferon alpha 7 [KO:K05414]
3445  IFNA8; interferon alpha 8 [KO:K05414]
3446  IFNA10; interferon alpha 10 [KO:K05414]
3447  IFNA13; interferon alpha 13 [KO:K05414]
3448  IFNA14; interferon alpha 14 [KO:K05414]
3449  IFNA16; interferon alpha 16 [KO:K05414]
3451  IFNA17; interferon alpha 17 [KO:K05414]
3452  IFNA21; interferon alpha 21 [KO:K05414]
3108  HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3122  HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
1493  CTLA4; cytotoxic T-lymphocyte associated protein 4 [KO:K06538]
7173  TPO; thyroid peroxidase [KO:K00431] [EC:1.11.1.8]
7038  TG; thyroglobulin [KO:K10809]
941  CD80; CD80 molecule [KO:K05412]
942  CD86; CD86 molecule [KO:K05413]
940  CD28; CD28 molecule [KO:K06470]
3558  IL2; interleukin 2 [KO:K05429]
3105  HLA-A; major histocompatibility complex, class I, A [KO:K06751]
3106  HLA-B; major histocompatibility complex, class I, B [KO:K06751]
3107  HLA-C; major histocompatibility complex, class I, C [KO:K06751]
3134  HLA-F; major histocompatibility complex, class I, F [KO:K06751]
3135  HLA-G; major histocompatibility complex, class I, G [KO:K06751]
3133  HLA-E; major histocompatibility complex, class I, E [KO:K06751]
356  FASLG; Fas ligand [KO:K04389]
355  FAS; Fas cell surface death receptor [KO:K04390]
5551  PRF1; perforin 1 [KO:K07818]
3002  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
959  CD40LG; CD40 ligand [KO:K03161]
958  CD40; CD40 molecule [KO:K03160]
3565  IL4; interleukin 4 [KO:K05430]
3567  IL5; interleukin 5 [KO:K05428]
3586  IL10; interleukin 10 [KO:K05443]
102723407  IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]
7253  TSHR; thyroid stimulating hormone receptor [KO:K04249]
1081  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
7252  TSHB; thyroid stimulating hormone subunit beta [KO:K05251]
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
hsa04210  Apoptosis
hsa04514  Cell adhesion molecules
hsa04610  Complement and coagulation cascades
hsa04612  Antigen processing and presentation
hsa04660  T cell receptor signaling pathway
hsa04662  B cell receptor signaling pathway
hsa04918  Thyroid hormone synthesis
KO pathway
ko05320   

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