KEGG PATHWAY: uah05320

KEGG

PATHWAY: uah05320

Entry

uah05320 Pathway

Name

Autoimmune thyroid disease - Ursus arctos horribilis

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

Autoimmune thyroid disease

Organism

Ursus arctos horribilis [GN:uah]

Gene

interferon alpha-1/2-like [KO:K05414]

interferon alpha-1/2-like [KO:K05414]

interferon alpha-1/2-like [KO:K05414]

interferon alpha-2-like [KO:K05414]

CTLA4; cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]

TPO; LOW QUALITY PROTEIN: thyroid peroxidase [KO:K00431] [EC:1.11.1.8]

TG; thyroglobulin [KO:K10809]

LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain-like [KO:K06752]

LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]

HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]

DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]

SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]

HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]

DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]

HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]

HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]

HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]

HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]

uncharacterized protein LOC113265359 [KO:K10785]

CD80; T-lymphocyte activation antigen CD80 [KO:K05412]

CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]

CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]

IL2; interleukin-2 [KO:K05429]

HLA class I histocompatibility antigen, A-11 alpha chain-like isoform X1 [KO:K06751]

saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]

LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, A-3 alpha chain [KO:K06751]

DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751]

HLA class I histocompatibility antigen, alpha chain G-like isoform X1 [KO:K06751]

LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, A-32 alpha chain-like [KO:K06751]

H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751]

FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]

FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]

PRF1; perforin-1 [KO:K07818]

granzyme B-like isoform X1 [KO:K01353] [EC:3.4.21.79]

CD40LG; CD40 ligand [KO:K03161]

CD40; tumor necrosis factor receptor superfamily member 5 isoform X1 [KO:K03160]

IL4; interleukin-4 [KO:K05430]

IL5; interleukin-5 [KO:K05428]

IL10; interleukin-10 [KO:K05443]

uncharacterized protein LOC113267145 [KO:K06856]

TSHR; thyrotropin receptor [KO:K04249]

CGA; glycoprotein hormones alpha chain [KO:K08522]

TSHB; thyrotropin subunit beta [KO:K05251]

Compound

Iodine

Thyroxine

Triiodothyronine

Amiodarone hydrochloride (JP17/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

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

Apoptosis

Cell adhesion molecules (CAMs)

Complement and coagulation cascades

Antigen processing and presentation

T cell receptor signaling pathway

B cell receptor signaling pathway

Thyroid hormone synthesis

KO pathway

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