Assay of antibodies directed against cell surface receptors.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
B Marcus-Samuels
Publications and source records attributed to B Marcus-Samuels.
Anti-receptor antibodies mimic the effect of insulin to down-regulate insulin receptors in cultured human lymphoblastoid (IM-9) cells.
Autoantibodies directed against the insulin receptor mimicked the effect of insulin to down-regulate insulin receptors in IM-9 cells. This down-regulation occurred at 37 C, but not at 15 or 22 C. As with insulin itself, antireceptor antibodies caused down-regulation by accelerating the rate of receptor degradation. Down-regulation induced by antireceptor antibody may play a role in desensitizing target cells to the effects of insulin.
Autoantibodies↗
Binding of insulin to its receptor impairs recognition by monoclonal anti-insulin antibodies.
The interaction between insulin and its receptor was investigated using both monoclonal and polyclonal anti-insulin antibodies. After covalent cross-linking of 125I-insulin to the insulin receptor on cultured human lymphocytes (IM-9 cells) using disuccinimidyl suberate, we inquired whether the insulin-receptor complex could be immunoprecipitated with anti-insulin antibodies. While a polyclonal guinea pig anti-insulin antiserum succeeded in immunoprecipitating receptor-bound 125I-insulin, binding to the receptor decreased the avidity of the antiserum for the insulin moiety by a factor of approximately 1000-fold. Sixteen distinct monoclonal murine anti-insulin antibodies were employed to immunoprecipitate receptor-bound 125I-insulin. Of these 16 monoclonal antibodies, only one (antibody 5.9F4) could be shown to recognize receptor-bound 125I-insulin. Moreover, even with antibody 5.9F4, binding of 125I-insulin to its receptor reduced the affinity of the antibody by a factor of 10- to 100-fold. These data strongly suggest that, when insulin binds to its receptor, the majority of the insulin molecule is unavailable for binding by anti-insulin antibodies. It seems likely that the hormone binding site on the receptor may be very large, thereby allowing for sequestration of the majority of the insulin molecule with relatively little of the hormone remaining exposed.
Animals↗
Hypoglycemia associated with antibodies to the insulin receptor.
Antibodies to the insulin receptor are insulinomimetic in vitro, although they generally induce insulin resistance in vivo. We report the novel case of a patient who presented with fasting hypoglycemia as the sole manifestation of autoantibodies to the insulin receptor. Prednisone therapy (120 mg per day) produced a rise in fasting glucose to more than 100 mg per deciliter (6 mmol per liter) within 48 hours, although there was no detectable change in the titer of antireceptor antibodies. After 10 weeks of therapy, the titer of antireceptor antibodies had fallen approximately 100-fold, and prednisone could be discontinued without recurrence of hypoglycemia. This case demonstrates that antireceptor antibodies must be considered in the differential diagnosis of hypoglycemia, especially in patients with other manifestations of autoimmunity.
Adipose Tissue↗