Autoantigens in thyroid diseases

Abstract

The autoantigens involved in autoimmune thyroid disease have now been extensively characterised, and the autoantibodies they evoke provide important aids to diagnosis, leading to early treatment of thyroid autoimmunity. The next stage in the puzzle is to determine towards which epitopes on the autoantigens the immune response is directed. We have already come a long way in the identification of immunodominant epitopes and have been able to identify one T cell epitope which has pathogenic capabilities. Identification of other T cell and B cell epitopes will help us understand the cell-mediated and humoral responses in greater detail and in time lead to more specific therapeutic intervention. A greater understanding of the mechanisms underlying one particular autoimmune disease will give us insights into other diseases, due to the belief that there may well be common underlying defects that, due to a multitude of factors, manifest as different diseases. The susceptibility factors in autoimmune thyroidits and autoimmune disease in general are very complex. A greater understanding is required of HLA associations and how particular peptides are presented in vivo. Are susceptible MHC types the ones capable of presenting the pathogenic peptides? Our major T cell thyroiditogenic epitope contains a T4 residue which accounts for over half the molecular weight of the peptide. Its structure is large and consists of a double benzene ring structure with four iodine atoms. It will be interesting to see how such a peptide can be presented and which residues bind T cell receptor or MHC. In summary we can say that autoimmune disease is due to a cocktail of factors which all contrive to tip the delicate balance of the immune system into an autoimmune state. HLA association may play a role in conferring an enhanced ability to select from a restricted repertoire of pathogenic epitopes, those epitopes perhaps only becoming available for presentation after interaction with environmental agents, whatever they may be. Following this, the normal regulation of self presentation and tolerance mechanisms break down and autoimmunity supervenes.

Thyroid Autoimmunity in Patients with Skin Disorders

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The early phase of psoriatic arthritis

“…The use of various techniques, including the assessment of family members at higher risk of disease, combined with the predictive value of some major histocompatibility complex class II associations and the ability to detect subclinical disease has permitted robust models that envisage the failure of immunological tolerance in the primary and secondary lymphoid organs with inflammatory processes supervening in a particular target organ at a later date 5 6. As a rule, disease-associated autoantibodies lead to a progressive and inexorable attack on an organ until it is completely functionless—for example, the β cells of the pancreas in diabetes and the thyroid in autoimmune thyroid disease 7. In the case of anticitrullinated protein antibody-positive rheumatoid arthritis, recent genetic studies have confirmed multiple associations with proteins that are largely related to T- and B-cell function, including protein tyrosine phosphatase, non-receptor type 22 (PTPN22) and cytotoxic T-lymphocyte antigen 4 (CTLA4),8–10 which vindicates the classic paradigm of a disease process that is genetically dependent on the failure of tolerance of the key effector cells of the adaptive immune response.…”

Herbal medicine Gamgungtang down-regulates autoimmunity through induction of TH2 cytokine production by lymphocytes in experimental thyroiditis model

“…There is a spectrum of human autoimmune thyroiditis in which antibodies and T-cells contribute differentially to the pathology (Dawe et al, 1993). A variety of animal models for experimental autoimmune thyroiditis (EAT) exist which may arise as a result of different mechanisms.…”