CIRCULATING IGA-LP COMPLEXES IN WATANABE HERITABLE HYPERLIPIDEMIC AND CHOLESTEROL-FED NZW RABBITS

Auto-immune immunoglobulin-lipoprotein complexes (Ig-Lp), as well as other modified lipoproteins, are activators of the transformation of macrophages into foam cells which may be the first step in atherogenesis. In humans circulating Ig-Lp have been demonstrated in autoimmune hyper- or dyslipidemia (AIH, DIH) and found to be associated with conditions related to atherosclerosis. Thus Ig-Lps may be significant and potentially primary atherogenic factors. In order to test this hypothesis we compared the distribution of Ig-Lps in 14 WHHL homozygote rabbits and in 15 normal fed and 8 cholesterol-fed NZW rabbits, all males aged 4-6 months. The Ig-Lps were detected by ELISA using 2 different capture anti-Lp and 4 indicator antibodies specific for either total Igs or the IgA, IgM or IgG classes. Some Ig-Lp of all classes were found in normal fed NZW. As compared with these normal levels, IgA-Lp are increased 2.5-fold in both the WHHL and the cholesterol-fed NZW rabbits (P = 0.0002). During cholesterol feeding the increase of IgA-Lp and total cholesterol and their decrease after returning to a normal diet were parallel in NZW rabbits, but their variation was mainly independent. IgM-Lp was also increased, but to a much lesser extent, in WHHL and in cholesterol-fed NZW. IgG-Lp was not increased in WHHL and only moderately increased in some of the cholesterol-fed NZW. The WHHL and the cholesterol-fed NZW rabbits did not differ by the IgA-Lp content of the serum, but the level of IgM-Lp was higher in the former. These results, together with the analysis of the correlations, suggest that the IgA-Lp may be, in rabbits as in humans, an atherogenic factor independent of the overall lipoprotein pattern, and of its origin. The data also suggest an intervention of the gut associated lymphoid tissue (GALT) in the increase of IgA-Lp induced by the cholesterol feeding. © 1990.