Criteria for identifying endogenous compounds as digoxin-like immunoreactive factors in humans

Endogenous digoxin-like immunoreactive factors (DLIF) are factors in plasma that interact with anti-digoxin antibodies. In this report we propose specific empirical criteria that must be satisfied by any group of endogenous compounds purported to account for DLIF activity in human plasma. These criteria include immunoreactive potency relative to existing physiologic concentrations as well as the biochemical and protein binding properties of these compounds. Recent studies have identified several congeners of fatty acids and phospholipids, hydrocortisone, and dehydroepiandrosterone-sulfate as compounds likely to account for DLIF activity in plasma. Using the above criteria we demonstrate that the highest reported plasma concentrations of these compounds combined account for less than 25% of DLIF reported in healthy adult subjects, less than 11% in newborns, less than 27% in pregnant women, and less than 39% in patients with renal failure. Human serum albumin at a concentration of 40 g/l completely abolished any detectable interaction of these compounds with both anti-digoxin antibodies or canine kidney Na/K-ATPase. The immunoreactive and physical properties of these compounds are also not consistent with those reported for DLIF. We conclude that these compounds do not account for the plasma DLIF concentrations measured in human subjects nor are they likely to play a role as specific endogenous regulators of Na/K-ATPase.