CHOLESTEROL DYNAMICS IN AUTOIMMUNE HYPERLIPIDEMIA

Abstract

A 69 yr old white male with autoimmune hyperlipidemia for 19 yr and characterized by high serum levels (1500-3400 mg/dl) of IgA [immunoglobulin A] firmly bound to very-low- and low-density lipoproteins (serum total cholesterol 852 .+-. 51 mg/dl, free cholesterol 340 .+-. 52 mg/dl, triglyceride 1638 .+-. 411 mg/dl, phospholipid 934 .+-. 84 mg/dl) received (i.v.) a tracer dose of cholesterol-4-14C. Serum cholesterol specific activity was followed for 337 days and analyzed by the following 2 methods: compartmental analysis which revealed the best fit of a 2-compartment model with rapidly exchangeable pool of 710 gm (2563% of the mean of 15 mormal subjects), slowly exchangeable pool of 317 gm (651%), mean transit time of 92.5 days (167%), turnover rate 9.23 gm/day (654%) and excretory coefficient of 0.013 (25%); a simulated 5-compartment model involving serum free, esterified, red blood cell, and rapidly and slowly exchangeable tissue cholesterols for which pool sizes of 17, 25, 2.4, 674 and 350 gm, respectively, were calculated, and a turnover rate of 9.44 gm/day was obtained which agreed well with that of the 2-compartment model. The extreme hyperlipoproteinemia and expanded body cholesterol pools were primarily due to the impairment of feedback control of cholesterol synthesis as a consequence of the complexing of lipoprotein and IgA.