The IgG subclass distribution of TSH receptor blocking antibodies in primary hypothyroidism

Abstract

Objective: TSH receptor stimulating antibodies are restricted to the IgG1 subclass suggesting an oligoclonal origin. We wished to determine whether thyroid stimulation blocking antibodies, which also bind to the TSH receptor but may cause hypothyroidism, are similarly IgG subclass restricted.

Design: Sera containing TSH receptor blocking antibody activity were separated into IgG subclasses by negative depletion of all other subclasses on affinity columns of subclass-specific monoclonal antibodies or protein A as appropriate.

Patients: Eleven patients from two centres were studied. All had autoimmune hypothyroidism and TSH receptor blocking antibodies but no thyroid stimulating antibodies.

Measurements: TSH receptor blocking antibody activity was measured by assessing inhibition of TSH-stimulated cAMP production by human thyroid cells (five Israeli samples) or by the FRTL-5 rat thyroid cell line (six Korean samples).

Results: IgG1 was the most important subclass containing TSH receptor blocking antibody activity but complete restriction to this subclass was never seen. Clearly detectable activity was found in the IgG2 subclass in eight patients, in the IgG3 subclass in three patients, and in the IgG4 subclass in six patients. The percentage recovery of activity in the sum of the separated fractions generally corresponded to the activity in whole immunoglobulin, being 117 +/- 66% in the nine patients in whom this could be assessed, although in one of these, the activities in the sum of the fractions was much higher (284%).

Conclusions: Unlike thyroid stimulating antibodies, thyroid stimulation blocking antibodies are not subclass restricted and are therefore likely to have a polyclonal origin. The IgG subclass distribution of these blocking antibodies resembles that of thyroglobulin and thyroid peroxidase antibodies.