Prevention and induction of occlusive coronary vascular disease in autoimmune (W/B)F1 mice by haploidentical bone marrow transplantation: possible role for anticardiolipin autoantibodies.
Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, thrombocytopenia, lupus nephritis, and coronary vascular disease with myocardial infarction (CVD). To determine whether this murine lupus-associated CVD could be transferred to otherwise autoimmune-resistant (C57BL/6 x C3H/He)F1 (B6C3F1) mice via W/BF1 T-cell-depleted marrow (TCDM) transplants, or conversely whether the CVD of W/BF1 mice could be prevented by the reciprocal transplant, reciprocal haploidentical transplants of TCDM were performed. CVD developed only in mice with systemic autoimmunity. Mice that developed lupus had glomerulonephritis and thrombocytopenia and also had elevated titres of autoantibodies to double-strand DNA, cardiolipin, and platelets and elevated levels of circulating immune complexes. Of control W/BF1 mice, 80% developed lupus, and of these, 81% developed CVD with a mean grade of 2.5 +/- 0.8. Engraftment of W/BF1 mice with B6C3F1 marrow protected 90% of the recipients from the development of lupus, and none developed CVD. Engraftment of B6C3F1 mice with W/BF1 marrow induced lupus in 60% of the recipients, and of those, 33% developed CVD with a mean grade of 1.3 +/- 0.3. The B6C3F1 recipients of W/BF1 marrow which developed CVD had significantly higher titres of autoantibodies to cardiolipin (aCL; P < .01). These findings show that genetic abnormalities present in the W/BF1 hematopoietic stem cells contribute to autoantibody development, including aCL, and suggest that thrombogenic mechanisms induced by aCL may contribute to the development of CVD in this form of murine lupus erythematosus.
Mizutani
H
H
Department of Pediatrics, University of South Florida, All Children's Hospital, St Petersburg 33701.
Engelman
R W
RW
Kinjoh
K
K
Kurata
Y
Y
Ikehara
S
S
Good
R A
RA
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000097:blood / Q000502:physiology*; D000936:Antigen-Antibody Complex / Q000097:blood; D001157:Arterial Occlusive Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D001327:Autoimmune Diseases / Q000150:complications*; D001792:Blood Platelets / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003327:Coronary Disease / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010976:Platelet Count
D017153:Antibodies, Anticardiolipin; D000936:Antigen-Antibody Complex