**4. Pathogenic mechanisms**

164 Thyroid Hormone

anti- thyroid drugs and radio-iodine.19, 20

**3.2. Assays for TSHR-Ab** 

*3.2.1. Radioreceptor assay* 

*3.2.2. In vitro bioassays* 

been solved in newer bioassays.

Majority of the T-lymphocytes are of TH1 subtype.26,27

*3.2.3. Cellular immunity* 

triiodothyronine level, serum thyroglobulin level and goiter size. TSAb are found in 90- 100% of untreated Graves' disease patients.17, 18 Level of TSAb decreases after treatment with

Two types of assays are used for TSHR-Ab-Radioreceptor assays and invitro bioassays.

generation radio-receptor assay has sensitivity of 99% and very high specificity. 21

Radioreceptor assay is most readily available and most widely used in clinical practice. Basic principle of radioreceptor assay is displacement of labeled TSH from solubilized TSHR from patient's serum. This TSH- binding inhibitory immunoglobulins (TBII) assay does not provide information regarding the functionality of TSHR-Ab. TBII assays are cheaper and having good precision. The first generation TBII assays have sensitivity of 75-95% in untreated Graves' disease patients. Most recently a monoclonal human antibody to TSHR is used. This second

In vitro bioassays are based on the ability of patients serum to stimulate adenylate cyclase and produce cAMP from cultured hamster ovary cells transfected with human TSHR (CHO-R),23 or rat thyroid cell strain (FRTL-5)24 or human thyroid follicular cells 25 are used as a source for functional TSHR. CHO-R system is slightly more sensitive, and requires an easier culture condition than other systems. Advantages of bioassays are that it gives information about the functional property of TSHR-Ab, but bioassays are more expensive, not widely available, having poor precision and sensitivity of more than 90%. These problems have

The thyroid gland in Graves' disease is characterized by non-homogenous lymphocytic infiltration. Majority of the intrathyroidal lymphocytes are T lymphocytes. B-lymphocytes are much less common than Hashimoto's thyroiditis. Cytokine profile produced by intrathyroidal T lymphocytes suggested that both TH1 & TH2 cells are present in thyroid.

TH1 cells are mainly involved in delayed type of hypersensitivity reactions, and it produces the cytokines like TNF-B, IFN-Y, IL-2, IL-10 and IL-17. TH1 cells are implicated in the pathogenesis of organ specific autoimmune diseases that is mediated mainly by TNF-β subtype, which uniquely produces IL-17. TH 2 cells are mainly responsible for humoral immune responses and they produce cytokines like IL-4, IL-5, IL-6 and IL-13.TH1 cells may also induce antibody formation through secretion of IL-10 28. IgG1 subclass of antibody are selectively induced by TH1 cells. Most of the intrathyroidal T cells are of memory (CD4+, CD29+) subtype. Concentration of cytotoxic T cells (CD8+) are much less in Graves' disease

### **4.1. Molecular mimicry or specificity crossover**

Structural or conformational similarity between different antigens like infectious agent with a self antigen can lead to crossover of specificity or molecular mimicry. Molecular mimicry has been reported between Reoviral antigen and a tissue antigen expressed in multiple endocrine tissues, Yersinia enterocolitica and TSHR, Retroviral sequences and TSHR & Borrelia and TSHR.
