Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with β2-glycoprotein I

Background: Atherosclerosis is considered analogous to chronic inflammatory diseases. Beta2-glycoprotein I (beta2GPI) is a phospholipid binding protein shown to serve as a target for prothrombotic antiphospholipid antibodies. It has recently been demonstrated to drive an immune mediated reaction and enhance murine atherosclerosis. Oral tolerance is a method in which feeding a given antigen, downregulates the respective immune responses towards it, and attenuates concomitant organ specific disorders. Herein, we tested the hypothesis, that inhibiting cellular immunity to beta2GPI Would result in suppression of fatty streak formation in mice. Methods and results: LDL receptor deficient mice were fed different doses of human or bovine beta2GP1 or BSA and than switched to an atherogenic diet. To determine the effect of feeding on lymph node proliferative indices, separate groups or mice were fed beta2GPI and then immunized with the respective antigen. Feeding either human or bovine beta2GPI was effective in attenuating atherosclerosis as compared to control fed animals. Oral feeding with of beta2GPI inhibited lymph node cell reactivity to beta2GPI in mice immunized against the human protein. Oral tolerance was also capable of reducing, reactivity to oxidized LDL in mice immunized against oxLDL. IL-4 and IL-10 production was Upregulated in lymph node cells of beta2GPI-tolerant mice immunized against beta2GPI, upon priming with the respective protein. Conclusion: Thus, oral administration of beta2GPI is an effective means Of Suppressing atherogenesis in mice and should further be investigated. (C) 2004 European Society of Cardiology. Published by Elsevier B.V.