Monoclonal anticardiolipin autoantibodies established from the (New Zealand white x BXSB)F1 mouse model of antiphospholipid syndrome cross-react with oxidized low-density lipoprotein.
OBJECTIVE
Autoimmunity-prone (New Zealand white x BXSB)F1 ([NZW x BXSB]F1) mice have been shown to be useful as a model of antiphospholipid syndrome with myocardial infarction. The aim of this study was to examine the cross-reactivity of anticardiolipin antibody (aCL) derived from (NZW x BXSB)F1 mice with oxidized low-density lipoprotein (ox-LDL), which is closely associated with atherosclerosis.


METHODS
Six monoclonal antibodies (MAb) against CL were established from (NZW x BXSB)F1 mice, and reactivity of aCL with ox-LDL was examined by micro-enzyme-linked immunosorbent assay.


RESULTS
Higher titers of anti-ox-LDL autoantibodies were found in adult (NZW x BXSB)F1 mice compared with other autoimmunity-prone mouse strains (P < 0.01) or a control strain (P < 0.005). There was a significant positive correlation between titers of aCL and those of anti-ox-LDL in (NZW x BXSB)F1 mice (r = 0.79, P < 0.001). Of the 6 MAb against CL, 2 clones that showed beta 2-glycoprotein 1-dependent reactivity also cross-reacted with ox-LDL. Binding of monoclonal aCL to solid-phase cardiolipin was inhibited by ox-LDL, but not by native LDL.


CONCLUSIONS
We confirmed that aCL derived from (NZW x BXSB)F1 mice can cross-react with ox-LDL. This result suggests that aCL, which is closely associated with lupus-associated thrombosis, may also play an important role in atherosclerotic complications in patients with systemic lupus erythematosus.
Mizutani
H
H
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Kurata
Y
Y
Kosugi
S
S
Shiraga
M
M
Kashiwagi
H
H
Tomiyama
Y
Y
Kanakura
Y
Y
Good
R A
RA
Matsuzawa
Y
Y
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000097:blood*; D000911:Antibodies, Monoclonal; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D003429:Cross Reactions / Q000276:immunology; D004195:Disease Models, Animal; D008077:Lipoproteins, LDL / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010084:Oxidation-Reduction
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D008077:Lipoproteins, LDL