Jack Leitch

Clinical Immunology

THYROID AUTOANTIBODIES

Briefly describe the thyroid and production of thyroid hormones

Understand some examples of thyroid disease and how they are categorised

Identify the main thyroid autoantibodies and how these are investigated in the laboratory

Understand how the main thyroid autoantibodies cause disease of the thyroid

AIMS

THE THYROID

HypothyroidismHashimoto’s disease

(1°autoimmune thyrioditis)

Diet (most common globally)

DrugsDamage1°/2°Congenital (rare)Adult Hypothyroidism 5x

more likely to affect women

THYROID DISEASE

HyperthyroidismGraves’ disease2° to another diseaseNodes (colloidal

thyroiditis)Adult Hyperthyroidism 7-

10x more likely to affect women

TPO - Thyroid peroxidase antibody Autoimmune thyroid disease (Hashimoto’s,

1°Myxoedema 90%)

TRAb – Thyroid stimulating hormone receptor antibodyGraves’ disease (Goitre)

TgAb - Thyroglobulin antibodyAutoimmune thyroid disease + monitoring thyroid

cancer treatment

AUTOANTIBODY TESTING

Antibody to glycoprotein (thyroperoxidase) responsible for catalysing iodine and performing iodination of tyrosine to produce thyroid hormones via colloid

Patient sample added to wells containing the thyroperoxidase protein

If there are antibodies present these will bind to the protein in the well

Labelled mouse anti-TPO is displacedThe light generated is inversely proportional to the

amount of patient TPO antibody present and boundMeasured with a luminometer (0-60 U/mL)

TPO

Hashimoto’s ≈ 90%Graves’ ≈ 60-80%10-12% of the healthy population may have

detectable anti-TPO antibodiesMainly used to help diagnose autoimmune thyroiditisAntibody titres can be done to assess disease activity

TPO

Antibody to TSH receptors in the thyroid. Defined by their action on signalling

Activating = stimulates (hyperthyroidism Graves’)Blocking = blocks receptor (Hypothyroidism

Hashimoto’s thyroiditis)Tubes coated with TSH receptorPatient sample incubated in tubes If antibody present the TSHr will be blockedLabelled anti-TSHr is then added to the tubes, which

will bind to any free TSHr in the tubeThe light emitted from these labelled antibodies is

measured via a luminometer>1.5 IU/L = positive

TRAB

These antibodies cause autoimmune thyrotoxicosisVery sensitive and specific for Graves’ disease

(>95%)Present in 70-100% of patients with Graves’Present in 1-2% of healthy populationMainly used when it is clinically indicated that the

patient may have Graves’ disease (detect or exclude)

TRAB

TRABAssay to become automatedWorks in a similar wayELISA platformCurrent method very time

consuming

Antibody targets thyroglobulinCan interfere with thyroglobulin quantificationSandwich assay (Immunoenzymatic) Sample added to wells with paramagnetic

thyroglobulinMagnetic field prevents Ag:Ab complex from washing

awayConjugate binds to TGAbChemiluminescent substrate binds to Conjugate<4 IU/mL

TGAB

High levels in the blood may indicate Graves’ or Hashimoto’s

Thyroid not normally released into the bloodstream30-50% with hypothyroidism will have these

antibodies15-30% with thyroid cancer will have these antibodies

TGAB

Generally, higher levels of antibody are indicative of an autoimmune thyroid disorder

Treatment often involves inhibiting an overactive thyroid, or replacing what is not being produced in an underactive thyroid

If severe inflammation occurs surgery may be neededAntibodies are organ specific, rather than systemicLaboratory testing key in diagnosis

CONCLUSION

Thank you

Tortora GJ, Derrickson B. The Endocrine System In: Tortora GJ, Derrickson B editors. Principles of Anatomy and Physiology [13 th Ed]. John Wiley & Sons; 2011. Pg:696-700.

Pyne D, Isenberg DA. Autoimmune Thyroid Disease in Systemic Lupus Erythematosus. Annals of the Rheumatic Diseases. 2001;61:70-72.

Murphy K, Travers P, Walport M. Autoimmunity and Transplantation In: Murphy K, Travers P, Walportm editors. Immunobiology [7 th Ed]. Garland Science; 2008. Pg:620-21.

Lab Tests Online[Internet]. London: The Association for Clinical Biochemistry and Laboratory Medicine; c2008 Oct. Thyroid Autoantibodies; 2008 [cited 2014 July 14]; [about 2 screens]. Available from http://labtestsonline.org.uk/understanding/analytes/thyroid-antibodies/tab/sample/

REFERENCES