Canis ISSN: 2398-2942

Thyroid: TgAA assay

Synonym(s): thyroglobulin autoantibodies, TGAA

Contributor(s): Vetstream Ltd, Roger Powell

Overview

  • Thyroglobulin is a 660kd protein as a 19S dimer that after deiodination and glycosylation acts as the major manufacture site and storage pool/form for T4 and T3 in the thyroid gland. 
  • During the process of inflammatory thyroid pathology (canine thyroiditis, equivalent to Hashimoto’s thyroiditis in humans), antibodies are generated against the largest protein mass within the thyroid gland, which is thyroglobulin. When TgAA develops at an epitope within the thyroglobulin molecule that contains a T3 or T4 storage site, the resulting TgAA will have cross reactivity to T3 or T4 respectively.  
  • Consequently, only a proportion of TgAAs will cross-react with the thyroid hormones. Antibodies that cross react with thyroxine (Thyroid: T4 assay) and tri-iodothyronine (Thyroid: T3 assay) are collectively known as thyroid hormone antibodies (THAA). These are subsets of thyroglobulin autoantibody (TgAA).  
  • Much (50-80%) of primary canine hypothyroidism Hypothyroidism is due to thyroid destruction via immune mediated lymphocytic thyroiditis, resulting in detectable levels of autoantibody against thyroglobulin (TgAA). 
  • They are more commonly seen in females and there appears to be a genetic predisposition with certain breeds being over-represented (eg Eurasiers Eurasier). 
  • The few veterinary studies have shown a varied prevalence of TgAA in 36-55% of hypothyroid dogs, THAA in 6-30% of hypothyroid dogs. 
  • In dogs with hypothyroidism, thyroglobulin autoantibodies of subclasses IgGI, IgG2 and IgG4 seem to predominate, IgG3 being much less common.

Sampling

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Tests

Methodologies

  • Unlike other THAAs (eg T3AA, T4AA Thyroid: T4 autoantibody assay), TgAA is species specific. 
  • TgAA can be detected in a variety of ways, including complement fixation, immunoprecipitation and EIAs Enzyme linked immunosorbent assay (ELISA), the last being the most common and widely utilized today.  
  • Initially these had variably high false positive rates. Newer methods are much better but are often still best run in duplicate with an average result reported if the two values measured are within accepted variance. If not, the testing should be repeated. 
  • Depends on laboratory and method or antibody kit used but reported relatively as a percentage (eg >25% or >35%), or via an equivalent “Positive/Inconclusive/Negative” result.  
  • Appropriate positive and negative controls should always be measured too so each test run is validated. 

Availability

  • Many commercial and specialist endocrine laboratories globally. 

Validity

  • Good precision and accuracy but these vary with laboratory and assay being used. Evaluation of an EIA (Oxford Laboratories Inc) compared to histopathologically confirmed thyroid disease was good.  
  • Some false positives (<10%) due to non-specific binding if the technique/assay does not eliminate this cross-reaction. 
  • As they are typically spectrophotometric at 450 nm, hemolysis and lipemia can significantly interfere to variably affect the measurements (increasing often, but also decreasing). 

Sensitivity

  • c. 90%. 

Specificity

  • c. 90%. 

Result Data

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Further Reading

Publications

Refereed Papers

  • Recent references from VetMed Resource and PubMed
  • Graham P A, Refsal K R, Nachreiner R F (2007) Etiopathologic findings of canine hypothyroidism. Vet Clin North Am Small Anim Pract 37(4), 617-631, v (Review) PubMed
  • Scott-Moncrieff J C et al (2002) Evaluation of antithyroglobulin antibodies after routine vaccination in pet and research dogs. JAVMA 221(4), 515-521 PubMed.  
  • Dixon R M, Mooney C T (1999) Canine serum thyroglobulin autoantibodies in health, hypothyroidism and non-thyroidal illness. Res VetSci 66(3), 243-246 PubMed
  • Day M J (1996) IgG subclasses of canine anti-erythrocyte, antinuclear and anti-thyroglobulin autoantibodies. Res Vet Sci 61(2),129-135 PubMed.  
  • Gaschen F, Thompson J, Beale K, Keisling K (1993) Recognition of triiodothyronine-containing epitopes in canine thyroglobulin by circulating thyroglobulin autoantibodies. Am J Vet Res 54(2), 244-247 PubMed
  • Thacker E L, Refsal K R, Bull R W (1992) Prevalence of autoantibodies to thyroglobulin, thyroxine, or triiodothyronine and relationship of autoantibodies and serum concentrations of iodothyronines in dogs. Am J Vet Res 53(4), 449-453 PubMed


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