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CURRENT INSIGHTS INTO THE "ANTIPHOSPHOLIPID" SYNDROME:
CLINICAL, IMMUNOLOGICAL, AND MOLECULAR ASPECTS
David A. Kandiah1, Andrej Sali2, Yonghua Sheng1, Edward J. Victoria3,
David M. Marquis3, Stephen M. Coutts 3 and Steven A. Krilis1
1Department of Immunology, Allergy and Infectious Disease, University
of New South Wales School of Medicine, St. George Hospital, Kogarah
2217, Australia; 2Rockefeller University, New York, NY 10021;3
La Jolla Pharmaceutical Company, San Diego, CA 92121
Advances in defining the target antigen(s) for the autoantibodies
in the APS highlight the inadequacies of the current classification
of these autoantibodies into anticardiolipin and LA antibodies.
The discovery that beta 2GPI is the target antigen for the autoantibodies
detected in solid-phase immunoassays has opened a number of areas
of research linking these autoantibodies to atherogenesis and
thrombus formation. Although the role of beta 2GPI in the regulation
of blood coagulation in unclear, current evidence suggests that
anti-beta 2GPI antibodies interfere with its "normal"
role and appear to promote a procoagulant tendency. The expansion
of research in this area and the diversity of the clinical manifestations
of patients with APS have resulted in the inclusion of molecular
biologists and pharmaceutical companies joining immunologists,
hematologists, rheumatologists, obstetricians, neurologists, vascular
surgeons, and protein and lipid biochemists in attempting to understand
the pathophysiology of this condition. Although the published
literature may result in conflicting results and introduce new
controversies, developing standardized laboratory methods and
extrapolation of in vitro experimental results to the vivo situation
will advance our understanding of the regulation of the immune
system and its interaction with normal hemostatic mechanisms.
Since the authors' last review in 1991, the study and understanding
of the pathophysiology of APS have evolved from lipid biochemistry
to molecular techniques that may eventually provide specific therapies
for the clinical manifestations of this condition. Although current
treatment has improved the morbidity associated with this condition,
especially in improving pregnancy outcomes, future therapies,
as outlined in this review, may specifically address the biological
abnormalities and have fewer side effects. Better diagnostic tools,
such as magnetic resonance imaging with perfusion studies, will
allow the study of the true incidence and prevalence of vascular
flow changes/tissue ischemia and infarction associated with aPL
antibodies and help determine treatment and prophylaxis for APS
patients. APS is still the only hypercoagulable condition where
both arterial and venous beds can be affected independently or
in the same individual.
Published in
Advances in Immunology
1998 70: 507-563
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