A human monoclonal antibody F_abreactive to oxidized LDL and carbamylated LDL recognizes human and mouse atherosclerotic lesions

Abstract

This study was undertaken to produce a F ab fragment of a human monoclonal antibody reactive to oxidized and carbamylated low-density lipoprotein (oxLDL and cLDL) using phage display technology. An analysis of DNA sequences of this F ab , termed plaque 15,16-46 F ab , revealed that the rearranged V H was highly mutated. Complementarity-determining regions of the V H showed a very high R/S ratio and contained many positively charged amino acids. In direct binding and competitive ELISA, the F ab reacted strongly with both MDA-LDL and Cu-oxLDL forms of oxLDL, and also showed high affinity for cLDL. Immunofluorescence and immunohistochemical analyses showed that this F ab positively stained atherosclerotic aortic plaques in ApoE (/ ( mice as well as those in patients with atherosclerosis. The F ab also showed positive staining in placental decidua from patients with preeclampsia. It is suggested that the plaque 15,16-46 F ab against oxLDL and cLDL might possibly be applicable for developing a diagnostic reagent for both human and rodent animal research to detect and characterize atherosclerotic disease progression in atherosclerotic lesions as well as exploring the pathogenesis of atherogenic diseases such as preeclampsia.