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 process have already been described. However, prospective data using in vivo markers and the influence of Cs-A in the oxidizability of low-density lipoprotein (LDL) are scarce. We aimed at investigating in this prospective study the evolution pattern of auto-antibodies directed against malondialdehyde-modified LDL (MDA-LDL) and Cu2+-oxidized LDL in 28 stable renal transplant recipients on Cs-A immunosuppressive therapy before and after 3 successive years of renal transplantation. Also, the effect of enrichment of LDL with Cs-A on the susceptibility of LDL to in vitro oxidation was tested. The results showed a significant increase of both auto-antibody titres (MDA-LDL and Cu2+-oxidized LDL) after 1 year, and the values remained high during the 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%, respectively. 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 changes during the lag phase in comparison with Cs-A-free LDL, indicating that Cs-A had no effect on in vitro LDL oxidizability. Our results suggest that Cs-A may be involved earlier in the LDL oxidation, but the mechanism by which it acts is still unclear.
Kandoussi
A M
AM
Institut Pasteur de Lille, Inserm U325, Lille, France. Abdelmejid.Kandoussi@pasteur-lille.fr
Glowacki
F
F
Duriez
P
P
Tacquet
A
A
Fruchart
J C
JC
Noël
C
C
D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D003300:Copper; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D008137:Longitudinal Studies; D008315:Malondialdehyde; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D006435:Renal Dialysis; D014181:Transplantation Immunology
D001323:Autoantibodies; D007166:Immunosuppressive Agents; D008055:Lipids; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde; D003300:Copper; D016572:Cyclosporine; C028419:cuprous chloride