KEGG   PATHWAY: rno05320
Entry
rno05320                    Pathway                                

Name
Autoimmune thyroid disease - Rattus norvegicus (rat)
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
rno05320  Autoimmune thyroid disease
rno05320

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
298205  Ifna4; interferon, alpha 4 precursor [KO:K05414]
298213  Ifna2; interferon alpha family, gene 2 precursor [KO:K05414]
298210  Ifna5; interferon alpha-1 precursor [KO:K05414]
690894  Ifna1; interferon alpha-5 [KO:K05414]
100912314  interferon alpha-1-like [KO:K05414]
502961  RGD1559679; interferon alpha-1-like [KO:K05414]
500491  Ifna16l1; interferon alpha-1-like [KO:K05414]
294274  RT1-DMa; RT1 class II, DM alpha precursor [KO:K06752]
294273  RT1-DMb; RT1 class II, DM beta precursor [KO:K06752]
24984  RT1-DOa; RT1 class II, locus DOa precursor [KO:K06752]
24986  RT1-Ha; RT1 class II, locus Ha precursor [KO:K06752]
294269  RT1-Da; RT1 class II, locus Da precursor [KO:K06752]
294270  RT1-Db1; rano class II histocompatibility antigen, D-1 beta chain precursor [KO:K06752]
309621  RT1-Ba; rano class II histocompatibility antigen, B alpha chain precursor [KO:K06752]
309622  RT1-Bb; rano class II histocompatibility antigen, B-1 beta chain precursor [KO:K06752]
365542  RT1-DOb; RT1 class II, DO beta [KO:K06752]
24981  RT1-Db2; RT1 class II, locus Db2 precursor [KO:K06752]
63835  Ctla4; cytotoxic T-lymphocyte protein 4 precursor [KO:K06538]
54314  Tpo; thyroid peroxidase precursor [KO:K00431] [EC:1.11.1.8]
24826  Tg; thyroglobulin isoform 2 precursor [KO:K10809]
25408  Cd80; T-lymphocyte activation antigen CD80 [KO:K05412]
56822  Cd86; T-lymphocyte activation antigen CD86 precursor [KO:K05413]
25660  Cd28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470]
116562  Il2; interleukin-2 precursor [KO:K05429]
24747  RT1-M3-1; RT1 class Ib, locus M3-1 precursor [KO:K06751]
24750  RT1-N3; RT1 class Ib, locus N3 [KO:K06751]
24973  RT1-A1; RT1 class Ia, locus A1 precursor [KO:K06751]
24974  RT1-A2; RT1 class Ia, locus A2 precursor [KO:K06751]
24988  RT1-M2; RT1 class Ib, locus M2 precursor [KO:K06751]
294213  RT1-M1-4; RT1 class I, locus M1, gene 4 precursor [KO:K06751]
309600  RT1-CE12; RT1 class I, locus CE12 precursor [KO:K06751]
309603  RT1-CE1; RT1 class I, locus CE1 precursor [KO:K06751]
309607  RT1-CE5; RT1 class I, locus CE5 isoform 1 precursor [KO:K06751]
309627  RT1-A3; RT1 class I, locus A3 precursor [KO:K06751]
361787  RT1-T24-1; RT1 class I, locus T24, gene 1 [KO:K06751]
365527  RT1-M6-2; RT1 class I, locus M6, gene 2 precursor [KO:K06751]
368153  RT1-CE7; RT1 class I, locus CE7 precursor [KO:K06751]
414270  RT1-CE14; RT1 class I, locus CE14 isoform 1 precursor [KO:K06751]
414779  RT1-CE2; RT1 class I, locus CE2 precursor [KO:K06751]
414783  RT1-CE4; RT1 class I, locus CE4 precursor [KO:K06751]
414784  RT1-T24-4; RT1 class I, locus T24, gene 4 [KO:K06751]
414785  RT1-M6-1; RT1 class I, locus M6, gene 1 precursor [KO:K06751]
414786  RT1-M1-2; RT1 class I, locus M1, gene 2 precursor [KO:K06751]
414787  RT1-M10-1; RT1 class I, locus M10, gene 1 precursor [KO:K06751]
414789  RT1-CE15; RT1 class I, locus CE15 precursor [KO:K06751]
414790  RT1-CE13; RT1 class I, locus CE13 precursor [KO:K06751]
414791  RT1-CE11; RT1 class I, locus CE11 precursor [KO:K06751]
414792  RT1-CE10; RT1 class I, locus CE10 precursor [KO:K06751]
414793  RT1-CE3; RT1 class I, locus CE3 precursor [KO:K06751]
414819  RT1-CE16; RT1 class I, locus CE16 precursor [KO:K06751]
24751  RT1-O1; RT1 class Ib, locus O1 [KO:K06751]
406194  RT1-T18; RT1 class Ib, locus T18 precursor [KO:K06751]
294228  RT1-S3; RT1 class Ib, locus S3 precursor [KO:K06751]
309584  RT1-M4; RT1 class Ib, locus M4 precursor [KO:K06751]
360323  RT1-N2; RT1 class Ib, locus N2 precursor [KO:K06751]
414788  RT1-T24-3; RT1 class I, locus T24, gene 3 [KO:K06751]
680842  RT1-M1-5; RT1 class I, M1, gene 5 precursor [KO:K06751]
102546590  patr class I histocompatibility antigen, A-126 alpha chain-like [KO:K06751]
499400  RT1-M5; RT1 class Ib, locus M5 isoform 2 precursor [KO:K06751]
25385  Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
246097  Fas; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
50669  Prf1; perforin-1 precursor [KO:K07818]
171528  Gzmb; granzyme-like protein 1 precursor [KO:K01353] [EC:3.4.21.79]
84349  Cd40lg; CD40 ligand [KO:K03161]
171369  Cd40; tumor necrosis factor receptor superfamily member 5 precursor [KO:K03160]
287287  Il4; interleukin-4 precursor [KO:K05430]
24497  Il5; interleukin-5 precursor [KO:K05428]
25325  Il10; interleukin-10 precursor [KO:K05443]
25360  Tshr; thyrotropin receptor precursor [KO:K04249]
116700  Cga; glycoprotein hormones alpha chain precursor [KO:K08522]
25653  Tshb; thyrotropin subunit beta precursor [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
rno04210  Apoptosis
rno04514  Cell adhesion molecules
rno04610  Complement and coagulation cascades
rno04612  Antigen processing and presentation
rno04660  T cell receptor signaling pathway
rno04662  B cell receptor signaling pathway
rno04918  Thyroid hormone synthesis
KO pathway
ko05320   

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