Significance of serum antibodies reactive with flavoprotein subunit of succinate dehydrogenase in thyroid associated orbitopathy

Hoşal, Banu M.; Swanson, Jil; Thompson, Charlotte; Kubota, Sumihisa; Gunji, Kazuaki; Kennerdell, John S.; Wall, Jack R.

doi:10.1136/bjo.83.5.605

Cited by 5 publications

(2 citation statements)

References 20 publications

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“…66 The presence of anti-TSH receptor antibodies, in particular TSI, 67 has been correlated with the presence of thyroid eye disease, even in the 10% of individuals who are biochemically euthyroid, although at levels lower than in hyperthyroid Graves' disease. [73][74][75] Antiflavoprotein and anti-G2 antibodies are most strongly, although not exclusively, associated with eye disease. 68,69 In our experience, Graves' patients with the most severe exopthalmos have thyrotropin-binding inhibiting immunoglobulins (TBII).…”

Section: Thyroid Autoantibodiesmentioning

confidence: 99%

“…TSH receptor autoantibodies may not be detected in some euthyroid patients with Graves' ophthalmopathy 67 and correlations with exopthalmos remain controversial. 75 Newborns of mothers with Graves' disease may develop transient hypothyroidism as often as hyperthyroidism, which will revert within 2 to 5 months as the mother's autoantibodies in the infant disappear. The presence of anti-thyroglobulin and anti-microsomal antibodies is even lower in patients with euthyroid eye disease and indeed, anti-thyroid peroxidase negativity has been suggested as a risk factor for ophthalmopathy, emphasizing the need for alternative markers.…”

Section: Thyroid Autoantibodiesmentioning

confidence: 99%

See 1 more Smart Citation

Autoimmune Endocrine Disorders

Ergun-Longmire¹,

Maclaren²

2016

Endocrinology: Adult and Pediatric

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Section: Thyroid Autoantibodiesmentioning

confidence: 99%

Section: Thyroid Autoantibodiesmentioning

confidence: 99%

Autoimmune Endocrine Disorders

Ergun-Longmire¹,

Maclaren²

2016

Endocrinology: Adult and Pediatric

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Eye muscle antibodies in Graves’ ophthalmopathy: Pathogenic or secondary epiphenomenon?

Mizokami

Salvi

Wall

2004

J Endocrinol Invest

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The extra ocular (eye) muscles are one of the principal tissues involved in the autoimmune-mediated inflammation of Graves' ophthalmopathy (GO). Several eye muscle proteins are targeted by autoantibodies or sensitized T lymphocytes, or both, and include: G2s, which is now identified as the terminal 141 amino acids of the winged-helix transcription factor FOXP1, the flavoprotein (Fp) subunit of the mitochondrial enzyme succinate dehydrogenase, the so-called "64kDa protein", a non-tissue specific membrane protein called 1D and the calcium binding protein calsequestrin. Of these, antibodies against G2s and Fp are the most sensitive markers of eye muscle damage in patients with thyroid autoimmunity even though neither antigen is specific to eye muscle and neither antibody is specific to GO. However, the recent finding that the calsequestrin gene is 4.7 times more expressed in eye muscles than other skeletal muscles suggests that we should reconsider the possible role of anti-calsequestrin autoantibodies in ophthalmopathy. GO may comprise two main subtypes with different pathogenetic mechanisms, namely ocular myopathy in which eye muscle inflammation predominates and congestive ophthalmopathy where inflammatory changes occur in the periorbital connective tissues in the absence of eye muscle dysfunction. Anti-G2s and anti-Fp antibodies are closely associated with the ocular myopathy subtype of GO while antibodies targeting type XIII collagen, the only member of the collagen family to have a transmembrane domain, are closely linked to congestive ophthalmopathy. Since both G2s and Fp are intracellular antigens it is unlikely that either antibody causes eye muscle fiber damage in GO, although a role in the later stages of the disease when the fiber has released its cellular contents has not been excluded. Eye muscle antibodies that are cytotoxic to eye muscle cells in antibody-dependent cell-mediated cytotoxicity (ADCC) are more likely to play a role in eye muscle fiber damage since they target a putative eye muscle cell membrane antigen, the identity of which is currently being investigated. While anti-G2s and anti-Fp antibodies are probably secondary to an underlying reaction, such as cytotoxic T lymphocyte targeting of an eye muscle membrane antigen that has yet to be identified, they are reliable markers of immunologically mediated eye muscle fiber damage in patients with Graves' hyperthyroidism. In conclusion, while a pathogenic role for eye muscle antibodies has not been excluded, they are most likely secondary to cytotoxic T cell reactions in GO and, as such, good markers of this autoimmune disease.

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Thyroid Autoantibodies

Saravanan¹,

Dayan²

2001

Endocrinology and Metabolism Clinics of North America

120

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Although assays to detect thyroid autoantibodies have been available for more than 40 years, their place in the clinical management of thyroid disease has remained controversial; however, novel automated detection techniques using recombinant antigens are increasing the sensitivity and specificity of the assays, particularly for antibodies to the TSH receptor. In addition, new antigenic targets have been defined including the sodium-iodide symporter and four eye muscle proteins targeted in Graves' ophthalmopathy. This article summarizes the immunobiology, assay methodology and prevalence in thyroid diseases of each of the major thyroid autoantibodies before discussing the clinical indications for their use in thyroid diseases.

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Significance of serum antibodies reactive with flavoprotein subunit of succinate dehydrogenase in thyroid associated orbitopathy

Cited by 5 publications

References 20 publications

Autoimmune Endocrine Disorders

Autoimmune Endocrine Disorders

Eye muscle antibodies in Graves’ ophthalmopathy: Pathogenic or secondary epiphenomenon?

Thyroid Autoantibodies

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