Thyroid Stimulating Immunoglobulin(TSI) in Graves' Disease.

ORIGINAL ARTICLE: Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample

“…There are several reports which suggest that TSHR autoantibodies with stimulating activity and with blocking activity can be present in the same serum sample 6–8 . Isolation of K1‐18 and K1‐70 from the same preparation of lymphocytes now provides proof of this concept.…”

“…The clinical symptoms observed in AITD are dependent in part at least on the relative concentrations and activities of blocking and stimulating autoantibodies in the serum at any one time (i.e. the sum of the activities of the autoantibodies present in the sera) 1,4–6 . Their combined effects on TSH interactions with the TSHR may also be a factor.…”

“…Stimulating TSHR autoantibodies cause hyperthyroidism, whereas the much rarer blocking type TSHR autoantibodies can cause hypothyroidism 1–3 . Also, spontaneous transitions in the activity of serum TSHR autoantibodies do occur, and this can be associated with changes in thyroid function 1,4–8 . There is also evidence that patient sera can contain a mixture of stimulating and blocking type TSHR autoantibodies 6–8 …”

Thyrotrophin receptor antibody concentration and activity, several years after treatment for Graves’ disease

“…The discrepancy between the numbers of subjects who were TRAb‐positive (30/66) and TSAb‐positive (21/30) in our study may be explained by the differences in heterogeneous TSHR autoantibody populations in patient sera. Patient sera have been shown to contain a mixture of TSHR autoantibodies with some sera possessing TSAb and TSBAb . The net activity of this TRAb in the bioassay is closely associated with but, distinct from, a measurement of total TRAb binding to the TSHR.…”

“…5 Instead, bioassays measuring the cAMP response to TRAb stimulation, or inhibition of TSH induced stimulation of TSH receptor (TSHR) using cells expressing the TSHR, remain an invaluable tool for differentiation between TSAb and TSBAb. Subjects with autoimmune thyroid disease (AITD) can have a mixture of TSAb and TSBAb, [6][7][8][9] and their clinical presentation depends in part on whether TSAb or TSBAb activity is predominant. 10 The fate of TRAb during and following GD treatment is an important aspect of the pathophysiology of GD and has been examined previously.…”