IMMUNOCHEMILUMINOMETRIC ASSAY WITH 2 MONOCLONAL-ANTIBODIES AGAINST THE N-TERMINAL SEQUENCE OF HUMAN PARATHYROID-HORMONE

We have developed an immunochemiluminometric assay (ICMA) with two mon oclonal antibodies for the N-terminal sequence of human parathyroid ho rmone (hPTH). One monoclonal antibody (A1-70) was physically adsorbed onto polystyrene beads, the other (B1-70) was labelled with acridinium ester and synthetic hPTH (1-38) was used as standard. This assay has cross-reactions with synthetic hPTH (1-34) and hPTH (1-84) but no cros s-reactions with hPTH (4-16), (28-48), (39-84), (44-68), (53-84) and h PTH-rP (1-86). The assay detection limit is 0.4 pmol/l. The normal ran ge is 1.3-12 pmol/l based on 72 normal volunteers. About 91% of study patients (n = 58) with surgically proven primary hyperparathyroidism ( 1 degrees HPT) had PTH values above normal and one of them showed a lo w normal intact PTH value but elevated PTH values with use of this ass ay. After immunoabsorption of plasma samples from patients with second ary hyperparathyroidism (2 degrees HPT) on hemodialysis with polystyre ne beads containing antibodies against hPTH (39-84), some patients sti ll showed significant amounts of PTH in this new ICMA but not intact P TH, The data reveal that significant amounts of amino-terminal immunor eactive PTH fragments rarely exist in 1 degrees HPT but are present in some patients with 2 degrees HPT. The major advantage of this assay i s to measure both amino-terminal PTH fragments and intact PTH with no interference from carboxy-terminal PTH fragments because two anti-N-te rminal hormone sequence monoclonal antibodies are used.