Cholesterol dynamics in autoimmune hyperlipidemia

A 69-year-old white male with autoimmune hyperlipidemia for 19 years characterized by high serum levels (1,5000 to 3,400 mg. per deciliter) of IgA firmly bound to very-low- and low-density lipoproteins (serum total cholesterol 852 +/- 51 mg./dl., free cholesterol 340 +/- 52, triglyceride 1638 +/- 411, phospholipid 934 +/- 84) received intravenously a tracer dose of cholesterol-4-14C. Serum cholesterol specific activity was followed for 337 days and analyzed by two methods: (1) compartmental analysis which revealed the best fit of a two-compartment model with rapidly exchangeable pool 710 gm. (2,563 per cent of the mean of 15 normal subjects), slowly exchangeable pool 317 gm. (651 per cent), mean transit time 92.5 days (167 per cent), turnover rate 9.23 gm. per day (654 per cent), and excretory coefficient 0.013 (25 per cent); (2) a simulated five-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 agreed well with that of the two-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.