A Novel in Vitro Assay Correlates Insulin Receptor Autoantibodies with Fasting Insulin in Type B Insulin Resistance

CONTEXT:Severe insulin resistance (IR) in the presence of insulin receptor autoantibodies (InsR-aAb) is known as type B insulin resistance (TBIR). Considerable progress in therapy has been achieved, but diagnosis and monitoring of InsR-aAb remains a challenge.OBJECTIVE:This work aimed to establish a robust in vitro method for InsR-Ab quantification.METHODS:Longitudinal serum samples from patients with TBIR at the National Institutes of Health were collected. A bridge-assay for InsR-aAb detection was established using recombinant human insulin receptor as bait and detector. Monoclonal antibodies served as positive controls for validation.RESULTS:The novel assay proved sensitive, robust, and passed quality control. The measured InsR-aAb from TBIR patients was associated with disease severity, decreased on treatment, and inhibited insulin signaling in vitro. Titers of InsR-aAb correlated positively to fasting insulin in patients.CONCLUSION:Quantification of InsR-aAb from serum samples via the novel in vitro assay enables identification of TBIR and monitoring of successful therapy.