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 (JP19/USP/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
102723407  [KO:K06856]
1081  CGA; glycoprotein hormones alpha chain isoform 2 precursor [KO:K08522]
1493  CTLA4; cytotoxic T-lymphocyte protein 4 isoform CTLA4-TM precursor [KO:K06538]
3002  GZMB; granzyme B isoform 1 preproprotein [KO:K01353] [EC:3.4.21.79]
3105  HLA-A; HLA class I histocompatibility antigen, A alpha chain isoform A*03:01:01:01 precursor [KO:K06751]
3106  HLA-B; major histocompatibility complex, class I, B precursor [KO:K06751]
3107  HLA-C; HLA class I histocompatibility antigen, C alpha chain precursor [KO:K06751]
3108  HLA-DMA; HLA class II histocompatibility antigen, DM alpha chain precursor [KO:K06752]
3109  HLA-DMB; HLA class II histocompatibility antigen, DM beta chain precursor [KO:K06752]
3111  HLA-DOA; HLA class II histocompatibility antigen, DO alpha chain precursor [KO:K06752]
3112  HLA-DOB; HLA class II histocompatibility antigen, DO beta chain precursor [KO:K06752]
3113  HLA-DPA1; HLA class II histocompatibility antigen, DP alpha 1 chain precursor [KO:K06752]
3115  HLA-DPB1; HLA class II histocompatibility antigen, DP beta 1 chain precursor [KO:K06752]
3117  HLA-DQA1; HLA class II histocompatibility antigen, DQ alpha 1 chain precursor [KO:K06752]
3118  HLA-DQA2; HLA class II histocompatibility antigen, DQ alpha 2 chain precursor [KO:K06752]
3119  HLA-DQB1; HLA class II histocompatibility antigen, DQ beta 1 chain isoform 2 precursor [KO:K06752]
3120  HLA-DQB2; HLA class II histocompatibility antigen, DQ beta 2 chain isoform 2 precursor [KO:K06752]
3122  HLA-DRA; HLA class II histocompatibility antigen, DR alpha chain precursor [KO:K06752]
3123  HLA-DRB1; major histocompatibility complex, class II, DR beta 1 precursor [KO:K06752]
3125  HLA-DRB3; major histocompatibility complex, class II, DR beta 3 precursor [KO:K06752]
3126  HLA-DRB4; major histocompatibility complex, class II, DR beta 4 precursor [KO:K06752]
3127  HLA-DRB5; major histocompatibility complex, class II, DR beta 5 precursor [KO:K06752]
3133  HLA-E; HLA class I histocompatibility antigen, alpha chain E precursor [KO:K06751]
3134  HLA-F; HLA class I histocompatibility antigen, alpha chain F isoform 2 precursor [KO:K06751]
3135  HLA-G; HLA class I histocompatibility antigen, alpha chain G isoform 2 precursor [KO:K06751]
3439  IFNA1; interferon alpha-1 precursor [KO:K05414]
3440  IFNA2; interferon alpha-2 precursor [KO:K05414]
3441  IFNA4; interferon alpha-4 precursor [KO:K05414]
3442  IFNA5; interferon alpha-5 precursor [KO:K05414]
3443  IFNA6; interferon alpha-6 precursor [KO:K05414]
3444  IFNA7; interferon alpha-7 precursor [KO:K05414]
3445  IFNA8; interferon alpha-8 precursor [KO:K05414]
3446  IFNA10; interferon alpha-10 precursor [KO:K05414]
3447  IFNA13; interferon alpha-13 precursor [KO:K05414]
3448  IFNA14; interferon alpha-14 precursor [KO:K05414]
3449  IFNA16; interferon alpha-16 precursor [KO:K05414]
3451  IFNA17; interferon alpha-17 precursor [KO:K05414]
3452  IFNA21; interferon alpha-21 precursor [KO:K05414]
355  FAS; tumor necrosis factor receptor superfamily member 6 isoform 1 precursor [KO:K04390]
3558  IL2; interleukin-2 precursor [KO:K05429]
356  FASLG; tumor necrosis factor ligand superfamily member 6 isoform 1 [KO:K04389]
3565  IL4; interleukin-4 isoform 1 precursor [KO:K05430]
3567  IL5; interleukin-5 precursor [KO:K05428]
3586  IL10; interleukin-10 isoform 1 precursor [KO:K05443]
5551  PRF1; perforin-1 precursor [KO:K07818]
7038  TG; thyroglobulin precursor [KO:K10809]
7173  TPO; thyroid peroxidase isoform a precursor [KO:K00431] [EC:1.11.1.8]
7252  TSHB; thyrotropin subunit beta isoform 1 precursor [KO:K05251]
7253  TSHR; thyrotropin receptor isoform 1 precursor [KO:K04249]
940  CD28; T-cell-specific surface glycoprotein CD28 isoform 1 precursor [KO:K06470]
941  CD80; T-lymphocyte activation antigen CD80 precursor [KO:K05412]
942  CD86; T-lymphocyte activation antigen CD86 isoform 1 precursor [KO:K05413]
958  CD40; tumor necrosis factor receptor superfamily member 5 isoform 1 precursor [KO:K03160]
959  CD40LG; CD40 ligand [KO:K03161]
Compound
C01382  Iodine
C01829  Thyroxine
C02465  Triiodothyronine
D00636  Amiodarone hydrochloride (JP19/USP)
Reference
PMID:15049952
  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
PMID:15762980
  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
PMID:11913070
  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
PMID:12192541
  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
PMID:11396701
  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
PMID:17192582
  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
PMID:15132715
  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
PMID:11577986
  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 molecule (CAM) interaction
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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