Monoclonal antiparathyroid antibodies revealing defect expression of a calcium receptor mechanism in hyperparathyroidism.

Abstract

AbstractMonoclonal antibodies were generated with a hybridoma technique after immunization of mice with intact human parathyroid cells. Three antibodies of the IgG type reacted in immunohistochemistry and immunofluorescense with parathyroid epithelial cells and proximal tubule cells of the kidney but not with a large number of other human tissues. Adenomatous and hyperplastic parathyroid glands of patients with hyperparathyroidism (HPT) demonstrated a reduced immunohistochemical reactivity with the antibodies as compared to the intense staining of normal human parathyroid tissue. Experiments with dispersed parathyroid cells from the normal and pathological glands showed that 2 of the antibodies blocked the effects of ambient calcium on cytoplasmic calcium and parathyroid hormone release. This indicates that the antibodies interfere with a newly recognized receptor mechanism of parathyroid cells involved in the sensing and gating of calcium and thereby also in the regulation of parathyroid hormone release. A reduced expression of the putative calcium receptor mechanism of abnormal parathyroid cells may, thus, be principally responsible for the hypercalcemia of HPT by causing a decreased sensitivity to extracellular calcium of the parathyroid hormone release from pathological parathyroid glands. The antibodies should improve the parathyroid histological diagnosis by their ability to identify and to distinguish between normal and abnormal parathyroid tissue.