Estimation of Serum TSH Receptor Autoantibody Concentration and Affinity

We have used the human monoclonal TSH receptor (TSHR) autoantibody (M22) as a labeled ligand in competition with individual patient TSHR autoantibodies (TRAb) to estimate their serum concentrations and affinities. TSHR coated tubes, 125I-labeled M22 IgG and Fab, and patient sera IgG and Fab were used in these studies. In 15 patients with Graves’ disease, TRAb concentrations ranged from 50 to 500 ng/mL of serum (5– 60 parts per million of total serum IgG) and TRAb IgG affinities from 3.0 ± 1.0–6.7 ± 1.54–1010 L/mol (mean ± SD; n=3). Fab fragment affinities were similar to those of intact IgG. Serum TRAb with blocking (TSH antagonist; 4 patients) activity had similar affinities (3.0 ± 0.25–7.2 ± 2.2–1010 L/mol) to TRAb IgG from patients with Graves’ disease, but blocking TRAb concentrations were higher (1.7 – 27 mg/mL of serum). The concentrations of TRAb that we observed in the sera of the 15 Graves’ patient (0.33 – 3.3 nmol/L) can be compared with that of circulating TSH. In particular, a serum TSH concen...