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Antithyroid autoantibodies

January 01, 1970

Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies, TPOAb), thyrotropin receptor antibodies (TRAb) and thyroglobulin antibodies (TgAb). TRAb's are subdivided into activating, blocking and neutral antibodies, depending on their effect on the TSH receptor. Anti-sodium/iodide (Anti–Na+/I−) symporter antibodies are a more recent discovery and their clinical relevance is still unknown. Graves' disease and Hashimoto's thyroiditis are commonly associated with the presence of anti-thyroid autoantibodies. Although there is overlap, anti-TPO antibodies are most commonly associated with Hashimoto's thyroiditis and activating TRAb's are most commonly associated with Graves' disease. Thyroid microsomal antibodies were a group of anti-thyroid antibodies; they were renamed after the identification of their target antigen (TPO).[1][2][3][4]

Subtypes edit

Anti-thyroid antibodies can be subdivided into groups according to their target antigen.

Anti-TPO antibodies edit

Anti-thyroid peroxidase (anti-TPO) antibodies are specific for the autoantigen TPO, a 105 kDa glycoprotein that catalyses iodine oxidation and thyroglobulin tyrosyl iodination reactions in the thyroid gland.[5] Most antibodies produced are directed to conformational epitopes of the immunogenic carboxyl-terminal region of the TPO protein, although antibodies to linear epitopes have been seen.[4] Anti-TPO antibodies are the most common anti-thyroid autoantibody, present in approximately 90% of Hashimoto's thyroiditis, 75% of Graves' disease and 10–20% of nodular goiter or thyroid carcinoma. Also, 10–15% of normal individuals can have high level anti-TPO antibody titres.[4][6][7] High serum antibodies are found in active phase chronic autoimmune thyroiditis. Thus, an antibody titer can be used to assess disease activity in patients that have developed such antibodies.[4][7][8] The majority of anti-TPO antibodies are produced by thyroid infiltrating lymphocytes, with minor contributions from lymph nodes and the bone marrow.[9] They cause thyroid cell damage by complement activation and antibody dependent cell cytotoxicity.[7] However, anti-TPO antibodies are not believed to contribute to the destruction of the thyroid.[10]

TSH receptor antibodies edit

The thyrotropin receptor (TSH receptor) is the antigen for TSH receptor antibodies (TRAbs). It is a seven transmembrane G protein-coupled receptor that is involved in thyroid hormone signalling. TRAbs are grouped depending on their effects on receptor signalling; activating antibodies (associated with hyperthyroidism), blocking antibodies (associated with thyroiditis) and neutral antibodies (no effect on receptor). Activating and blocking antibodies mostly bind to conformational epitopes, whereas neutral antibodies bind to linear epitopes. Binding of the antibody to the amino terminus of the TSH receptor shows stimulatory activity, whereas binding to residues 261-370 or 388-403 block the activity. TRAbs are present in 70–100% of Graves' disease (85–100% for activating antibodies and 75–96% for blocking antibodies) and 1–2% of normal individuals.[1][2][11]

Activating TRAbs are characteristic of Graves' disease (autoimmune hyperthyroidism). TPO antibody is measured more easily than the TSH receptor antibody, and so is often used as a surrogate in the diagnosis of Graves' disease. These antibodies activate adenylate cyclase by binding to the TSH receptor. This causes the production of thyroid hormones and subsequent growth and vascularisation of the thyroid.[1] TRAbs are also useful in the diagnosis of Graves' ophthalmopathy. Although the exact mechanism of how TRAbs induce Graves' ophthalmopathy is unknown, it is likely that the antibodies bind to TSH receptors in retro-orbital tissues, causing infiltration of lymphocytes. This inflammatory response leads to cytokine production that causes fibroblasts to produce glycosaminoglycans, leading to ophthalmopathy.[12][13]

Blocking TRAbs (also known as thyrotropin binding inhibitory immunoglobulins (TBII)) competitively block the activity of TSH on the receptor. This can cause hypothyroidism by reducing the thyrotropic effects of TSH. They are found in Hashimoto's thyroiditis and Graves' disease and may be cause of fluctuation of thyroid function in the latter. During treatment of Graves' disease they may also become the predominant antibody, which can cause hypothyroidism.[2][13]

The clinical and physiological relevance of neutral antibodies remains unclear. However, they may be involved in prolonging the TSH receptor half-life.[2]

Thyroglobulin (TG) antibodies edit

Thyroglobulin antibodies are specific for thyroglobulin, a 660 kDa matrix protein involved in the process of thyroid hormone production. They are found in 70% of Hashimoto's thyroiditis, 60% of idiopathic hypothyroidism, 30% of Graves' disease, a small proportion of thyroid carcinoma and 3% of normal individuals.[1][3] Anti-TPO antibodies are present in 99% of cases where thyroglobulin antibodies are present, however only 35% of anti-TPO antibody positive cases also demonstrate thyroglobulin antibodies.[14]

Anti–Na+/ I− symporter edit

Anti-Na+/I− symporter antibodies are a more recent discovery of possible thyroid autoantibodies and their role in thyroid disease remains uncertain. They are present in approximately 20% of Graves' disease and 24% of Hashimoto's thyroiditis.[1]

Pathogenesis edit

The production of antibodies in Graves' disease is thought to arise by activation of CD4+ T-cells, followed by B-cell recruitment into the thyroid. These B-cells produce antibodies specific to the thyroid antigens. In Hashimoto's thyroiditis, activated CD4+ T-cells produce interferon-γ, causing the thyroid cells to display MHC class II molecules. This expands the autoreactive T-cell repertoire and prolongs the inflammatory response.[15]

While anti-thyroid antibodies are used to track the presence of autoimmune thyroiditis, they are generally not considered to contribute directly to the destruction of the thyroid.[10]

Effect on human reproduction edit

The presence of anti-thyroid antibodies is associated with an increased risk of unexplained subfertility (odds ratio 1.5 and 95% confidence interval 1.1–2.0), miscarriage (odds ratio 3.73, 95% confidence interval 1.8–7.6), recurrent miscarriage (odds ratio 2.3, 95% confidence interval 1.5–3.5), preterm birth (odds ratio 1.9, 95% confidence interval 1.1–3.5) and maternal postpartum thyroiditis (odds ratio 11.5, 95% confidence interval 5.6–24).[16]

History edit

In 1912 Hakaru Hashimoto described hypothyroidism and goiter associated with thyroid lymphoid infiltration. In 1956 the anti-Tg antibody was detected in similar cases, elucidating the autoimmune cause of these characteristics. Later the same year, activating TSH receptor antibodies were discovered. Thyroid microsomal antibodies were discovered in 1964, which were subsequently renamed anti-TPO antibodies due to the identification of their autoantigen.[1]

References edit

  1. ^ a b c d e f Saravanan P, Dayan CM (June 2001). "Thyroid autoantibodies". Endocrinology and Metabolism Clinics of North America. 30 (2): 315–37, viii. doi:10.1016/S0889-8529(05)70189-4. PMID 11444165.
  2. ^ a b c d Orgiazzi J (June 2000). "Anti-TSH receptor antibodies in clinical practice". Endocrinology and Metabolism Clinics of North America. 29 (2): 339–55, vii. doi:10.1016/S0889-8529(05)70135-3. PMID 10874533.
  3. ^ a b Boyd CM, Baker JR (March 1996). "The immunology of thyroid cancer". Endocrinology and Metabolism Clinics of North America. 25 (1): 159–79. doi:10.1016/S0889-8529(05)70317-0. PMID 8907685.
  4. ^ a b c d Utiger LE, Braverman RD (2005). Werner & Ingbar's the thyroid : a fundamental and clinical text (9th ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0781750474.
  5. ^ Taurog A (May 1999). "Molecular evolution of thyroid peroxidase". Biochimie. 81 (5): 557–62. doi:10.1016/S0300-9084(99)80110-2. PMID 10403190.
  6. ^ Saravanan P, Dayan CM (June 2001). "Thyroid autoantibodies". Endocrinology and Metabolism Clinics of North America. 30 (2): 315–37, viii. doi:10.1016/S0889-8529(05)70189-4. PMID 11444165.
  7. ^ a b c Chardès T, Chapal N, Bresson D, Bès C, Giudicelli V, Lefranc MP, Péraldi-Roux S (June 2002). "The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases". Immunogenetics. 54 (3): 141–57. doi:10.1007/s00251-002-0453-9. PMID 12073143. S2CID 2701974.
  8. ^ McLachlan SM, Rapoport B (2000). "Autoimmune response to the thyroid in humans: thyroid peroxidase--the common autoantigenic denominator". International Reviews of Immunology. 19 (6): 587–618. doi:10.3109/08830180009088514. PMID 11129117. S2CID 11431166.
  9. ^ Trbojević B, Djurica S (October 2005). "[Diagnosis of autoimmune thyroid disease]". Srpski Arhiv Za Celokupno Lekarstvo. 133 (Suppl 1): 25–33. doi:10.2298/sarh05s1025t. PMID 16405253.
  10. ^ a b Melmed S (2011). Williams Textbook of Endocrinology (12th ed.). Philadelphia: Elsevier/Saunders. p. 355. ISBN 978-1-4377-0324-5.
  11. ^ Swain M, Swain T, Mohanty BK (January 2005). "Autoimmune thyroid disorders-An update". Indian Journal of Clinical Biochemistry. 20 (1): 9–17. doi:10.1007/BF02893034. PMC 3454167. PMID 23105486.
  12. ^ Nayak B, Hodak SP (September 2007). "Hyperthyroidism". Endocrinology and Metabolism Clinics of North America. 36 (3): 617–56, v. doi:10.1016/j.ecl.2007.06.002. PMID 17673122.
  13. ^ a b Kamath C, Adlan MA, Premawardhana LD (2012). "The role of thyrotrophin receptor antibody assays in graves' disease". Journal of Thyroid Research. 2012: 525936. doi:10.1155/2012/525936. PMC 3345237. PMID 22577596.
  14. ^ Ai J, Leonhardt JM, Heymann WR (May 2003). "Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations". Journal of the American Academy of Dermatology. 48 (5): 641–59, quiz 660–2. doi:10.1067/mjd.2003.257. PMID 12734493.
  15. ^ Stassi G, De Maria R (March 2002). "Autoimmune thyroid disease: new models of cell death in autoimmunity". Nature Reviews. Immunology. 2 (3): 195–204. doi:10.1038/nri750. PMID 11913070. S2CID 7434981.
  16. ^ van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, Bisschop PH (2011). "Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review". Human Reproduction Update. 17 (5): 605–19. doi:10.1093/humupd/dmr024. PMID 21622978.

January 01, 1970
antithyroid, autoantibodies, simply, antithyroid, antibodies, autoantibodies, targeted, against, more, components, thyroid, most, clinically, relevant, anti, thyroid, autoantibodies, anti, thyroid, peroxidase, antibodies, anti, antibodies, tpoab, thyrotropin, . Antithyroid autoantibodies or simply antithyroid antibodies are autoantibodies targeted against one or more components on the thyroid The most clinically relevant anti thyroid autoantibodies are anti thyroid peroxidase antibodies anti TPO antibodies TPOAb thyrotropin receptor antibodies TRAb and thyroglobulin antibodies TgAb TRAb s are subdivided into activating blocking and neutral antibodies depending on their effect on the TSH receptor Anti sodium iodide Anti Na I symporter antibodies are a more recent discovery and their clinical relevance is still unknown Graves disease and Hashimoto s thyroiditis are commonly associated with the presence of anti thyroid autoantibodies Although there is overlap anti TPO antibodies are most commonly associated with Hashimoto s thyroiditis and activating TRAb s are most commonly associated with Graves disease Thyroid microsomal antibodies were a group of anti thyroid antibodies they were renamed after the identification of their target antigen TPO 1 2 3 4 Contents 1 Subtypes 1 1 Anti TPO antibodies 1 2 TSH receptor antibodies 1 3 Thyroglobulin TG antibodies 1 4 Anti Na I symporter 2 Pathogenesis 3 Effect on human reproduction 4 History 5 ReferencesSubtypes editAnti thyroid antibodies can be subdivided into groups according to their target antigen Anti TPO antibodies edit Anti thyroid peroxidase anti TPO antibodies are specific for the autoantigen TPO a 105 kDa glycoprotein that catalyses iodine oxidation and thyroglobulin tyrosyl iodination reactions in the thyroid gland 5 Most antibodies produced are directed to conformational epitopes of the immunogenic carboxyl terminal region of the TPO protein although antibodies to linear epitopes have been seen 4 Anti TPO antibodies are the most common anti thyroid autoantibody present in approximately 90 of Hashimoto s thyroiditis 75 of Graves disease and 10 20 of nodular goiter or thyroid carcinoma Also 10 15 of normal individuals can have high level anti TPO antibody titres 4 6 7 High serum antibodies are found in active phase chronic autoimmune thyroiditis Thus an antibody titer can be used to assess disease activity in patients that have developed such antibodies 4 7 8 The majority of anti TPO antibodies are produced by thyroid infiltrating lymphocytes with minor contributions from lymph nodes and the bone marrow 9 They cause thyroid cell damage by complement activation and antibody dependent cell cytotoxicity 7 However anti TPO antibodies are not believed to contribute to the destruction of the thyroid 10 TSH receptor antibodies edit The thyrotropin receptor TSH receptor is the antigen for TSH receptor antibodies TRAbs It is a seven transmembrane G protein coupled receptor that is involved in thyroid hormone signalling TRAbs are grouped depending on their effects on receptor signalling activating antibodies associated with hyperthyroidism blocking antibodies associated with thyroiditis and neutral antibodies no effect on receptor Activating and blocking antibodies mostly bind to conformational epitopes whereas neutral antibodies bind to linear epitopes Binding of the antibody to the amino terminus of the TSH receptor shows stimulatory activity whereas binding to residues 261 370 or 388 403 block the activity TRAbs are present in 70 100 of Graves disease 85 100 for activating antibodies and 75 96 for blocking antibodies and 1 2 of normal individuals 1 2 11 Activating TRAbs are characteristic of Graves disease autoimmune hyperthyroidism TPO antibody is measured more easily than the TSH receptor antibody and so is often used as a surrogate in the diagnosis of Graves disease These antibodies activate adenylate cyclase by binding to the TSH receptor This causes the production of thyroid hormones and subsequent growth and vascularisation of the thyroid 1 TRAbs are also useful in the diagnosis of Graves ophthalmopathy Although the exact mechanism of how TRAbs induce Graves ophthalmopathy is unknown it is likely that the antibodies bind to TSH receptors in retro orbital tissues causing infiltration of lymphocytes This inflammatory response leads to cytokine production that causes fibroblasts to produce glycosaminoglycans leading to ophthalmopathy 12 13 Blocking TRAbs also known as thyrotropin binding inhibitory immunoglobulins TBII competitively block the activity of TSH on the receptor This can cause hypothyroidism by reducing the thyrotropic effects of TSH They are found in Hashimoto s thyroiditis and Graves disease and may be cause of fluctuation of thyroid function in the latter During treatment of Graves disease they may also become the predominant antibody which can cause hypothyroidism 2 13 The clinical and physiological relevance of neutral antibodies remains unclear However they may be involved in prolonging the TSH receptor half life 2 Thyroglobulin TG antibodies edit Thyroglobulin antibodies are specific for thyroglobulin a 660 kDa matrix protein involved in the process of thyroid hormone production They are found in 70 of Hashimoto s thyroiditis 60 of idiopathic hypothyroidism 30 of Graves disease a small proportion of thyroid carcinoma and 3 of normal individuals 1 3 Anti TPO antibodies are present in 99 of cases where thyroglobulin antibodies are present however only 35 of anti TPO antibody positive cases also demonstrate thyroglobulin antibodies 14 Anti Na I symporter edit Anti Na I symporter antibodies are a more recent discovery of possible thyroid autoantibodies and their role in thyroid disease remains uncertain They are present in approximately 20 of Graves disease and 24 of Hashimoto s thyroiditis 1 Pathogenesis editThe production of antibodies in Graves disease is thought to arise by activation of CD4 T cells followed by B cell recruitment into the thyroid These B cells produce antibodies specific to the thyroid antigens In Hashimoto s thyroiditis activated CD4 T cells produce interferon g causing the thyroid cells to display MHC class II molecules This expands the autoreactive T cell repertoire and prolongs the inflammatory response 15 While anti thyroid antibodies are used to track the presence of autoimmune thyroiditis they are generally not considered to contribute directly to the destruction of the thyroid 10 Effect on human reproduction editThe presence of anti thyroid antibodies is associated with an increased risk of unexplained subfertility odds ratio 1 5 and 95 confidence interval 1 1 2 0 miscarriage odds ratio 3 73 95 confidence interval 1 8 7 6 recurrent miscarriage odds ratio 2 3 95 confidence interval 1 5 3 5 preterm birth odds ratio 1 9 95 confidence interval 1 1 3 5 and maternal postpartum thyroiditis odds ratio 11 5 95 confidence interval 5 6 24 16 History editIn 1912 Hakaru Hashimoto described hypothyroidism and goiter associated with thyroid lymphoid infiltration In 1956 the anti Tg antibody was detected in similar cases elucidating the autoimmune cause of these characteristics Later the same year activating TSH receptor antibodies were discovered Thyroid microsomal antibodies were discovered in 1964 which were subsequently renamed anti TPO antibodies due to the identification of their autoantigen 1 References edit a b c d e f Saravanan P Dayan CM June 2001 Thyroid autoantibodies Endocrinology and Metabolism Clinics of North America 30 2 315 37 viii doi 10 1016 S0889 8529 05 70189 4 PMID 11444165 a b c d Orgiazzi J June 2000 Anti TSH receptor antibodies in clinical practice Endocrinology and Metabolism Clinics of North America 29 2 339 55 vii doi 10 1016 S0889 8529 05 70135 3 PMID 10874533 a b Boyd CM Baker JR March 1996 The immunology of thyroid cancer Endocrinology and Metabolism Clinics of North America 25 1 159 79 doi 10 1016 S0889 8529 05 70317 0 PMID 8907685 a b c d Utiger LE Braverman RD 2005 Werner amp Ingbar s the thyroid a fundamental and clinical text 9th ed Philadelphia Lippincott Williams amp Wilkins ISBN 0781750474 Taurog A May 1999 Molecular evolution of thyroid peroxidase Biochimie 81 5 557 62 doi 10 1016 S0300 9084 99 80110 2 PMID 10403190 Saravanan P Dayan CM June 2001 Thyroid autoantibodies Endocrinology and Metabolism Clinics of North America 30 2 315 37 viii doi 10 1016 S0889 8529 05 70189 4 PMID 11444165 a b c Chardes T Chapal N Bresson D Bes C Giudicelli V Lefranc MP Peraldi Roux S June 2002 The human anti thyroid peroxidase autoantibody repertoire in Graves and Hashimoto s autoimmune thyroid diseases Immunogenetics 54 3 141 57 doi 10 1007 s00251 002 0453 9 PMID 12073143 S2CID 2701974 McLachlan SM Rapoport B 2000 Autoimmune response to the thyroid in humans thyroid peroxidase the common autoantigenic denominator International Reviews of Immunology 19 6 587 618 doi 10 3109 08830180009088514 PMID 11129117 S2CID 11431166 Trbojevic B Djurica S October 2005 Diagnosis of autoimmune thyroid disease Srpski Arhiv Za Celokupno Lekarstvo 133 Suppl 1 25 33 doi 10 2298 sarh05s1025t PMID 16405253 a b Melmed S 2011 Williams Textbook of Endocrinology 12th ed Philadelphia Elsevier Saunders p 355 ISBN 978 1 4377 0324 5 Swain M Swain T Mohanty BK January 2005 Autoimmune thyroid disorders An update Indian Journal of Clinical Biochemistry 20 1 9 17 doi 10 1007 BF02893034 PMC 3454167 PMID 23105486 Nayak B Hodak SP September 2007 Hyperthyroidism Endocrinology and Metabolism Clinics of North America 36 3 617 56 v doi 10 1016 j ecl 2007 06 002 PMID 17673122 a b Kamath C Adlan MA Premawardhana LD 2012 The role of thyrotrophin receptor antibody assays in graves disease Journal of Thyroid Research 2012 525936 doi 10 1155 2012 525936 PMC 3345237 PMID 22577596 Ai J Leonhardt JM Heymann WR May 2003 Autoimmune thyroid diseases etiology pathogenesis and dermatologic manifestations Journal of the American Academy of Dermatology 48 5 641 59 quiz 660 2 doi 10 1067 mjd 2003 257 PMID 12734493 Stassi G De Maria R March 2002 Autoimmune thyroid disease new models of cell death in autoimmunity Nature Reviews Immunology 2 3 195 204 doi 10 1038 nri750 PMID 11913070 S2CID 7434981 van den Boogaard E Vissenberg R Land JA van Wely M van der Post JA Goddijn M Bisschop PH 2011 Significance of sub clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy a systematic review Human Reproduction Update 17 5 605 19 doi 10 1093 humupd dmr024 PMID 21622978 Retrieved from https en wikipedia org w index php title Antithyroid autoantibodies amp oldid 1187876734, wikipedia, wiki, book, books, library,

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