Cell-based bioassays are used to determine the biological activity of complex biotherapeutic products, to assign potency and to assure the quality and consistency of the manufacturing process. Clinically, these assays are used to assess bioactivity in patient samples, particularly for the detection of antidrug neutralizing antibodies. Owing to their versatility, cellular assays that measure endogenous gene expression by quantitative reverse transcription PCR offer a rapid and automatable alternative to assays measuring functional, late-stage responses. Notably, detection of immediate early gene expression represents a direct response of the cell to receptor ligation by the biotherapeutic. We review current developments in the use of this approach and demonstrate its application to the detection of receptor-binding autoantibodies using, as a case study, the detection of autoantibodies to the thyroid-stimulating hormone receptor.