Evolution pattern of auto-antibodies against oxidized low-density lipoproteins in renal transplant recipients

An increased degree of oxidative stress in renal transplant recipients and a possible role of ciclosporin A (Cs-A) immunosuppressive therapy in this p rocess have already been described. However, prospective data using in vivo markers and the influence of Cs-A in the oxidizability of low-density lipo protein (LDL) are scarce. We aimed at investigating in this prospective stu dy the evolution pattern of auto-antibodies directed against malondialdehyd e-modified LDL (MDA-LDL) and Cu2+-oxidized LDL in 28 stable renal transplan t recipients on Cs-A immunosuppressive therapy before and after 3 successiv e years of renal transplantation. Also, the effect of enrichment of LDL wit h Cs-A on the susceptibility of LDL to in vitro oxidation was tested. The r esults showed a significant increase of both auto-antibody titres (MDA-LDL and Cu2+-oxidized LDL) after 1 year, and the values remained high during th e 2nd and the 3rd year following transplantation. The yearly mean relative variations of auto-antibodies against MDA-LDL and Cu2+-oxidized LDL during the follow-up period were 133, 149, and 137%, and 111, 115, and 117%, respe ctively. A significant correlation was observed during the 1st year between Cs-A trough blood level and Cu2+-oxidized LDL auto-antibody: r = 0.04 (p = 0.046). Incorporation of Cs-A into LDL from healthy volunteers showed no c hanges during the lag phase in comparison with Cs-A-free LDL, indicating th at Cs-A had no effect on in vitro LDL oxidizability. Our results suggest th at Cs-A may be involved earlier in the LDL oxidation, but the mechanism by which it acts is still unclear. Copyright (C) 2001 S. Karger AG, Basel.