CTLA4Ig prevents initiation but not evolution of anti-phospholipid syndrome in NZW/BXSB mice.
NZW "x" BXSB F1 mice develop SLE that is associated with an anti-phospholipid syndrome characterized by anti-cardiolipin antibodies, thrombocytopenia and small coronary artery thrombosis. This syndrome is immune mediated and, dependent, on CD4+T cells. To determine whether disease in these mice can be treated with blockade of T cell costimulation we treated them with the CD28 antagonist CTLA4Ig at 9 or 12 weeks of age. CTLA4Ig completely prevented both SLE nephritis and myocardial infarcts if it was given at 9 weeks of age, before anti-cardiolipin antibodies could be detected in the serum and prevented both B cell expansion and activation and the development of peripheral monocytosis. If treatment was delayed until 12 weeks of age after cardiolipin antibodies had arisen but before the onset of clinical disease, CTLA4Ig had very little effect on disease progression. These findings indicate that CD4+T cell activation through CD28 is critical for disease initiation in this model but plays little role in disease progression or tissue damage. These findings have relevance to the treatment of anti-phospholipid syndrome in humans.
Akkerman
Alla
A
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Huang
Weiqing
W
Wang
Xiaobo
X
Ramanujam
Meera
M
Schiffer
Lena
L
Madaio
Michael
M
Factor
Stephen M
SM
Davidson
Anne
A
D000069594:Abatacept; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016736:Antiphospholipid Syndrome / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006321:Heart / Q000187:drug effects; D018796:Immunoconjugates / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D018796:Immunoconjugates; D000069594:Abatacept