Lisa R. Sammaritano, MD
Antiphospholipid antibodies (aPL) are associated with a clinical syndrome which includes recurrent arterial and venous thromboses, recurrent fetal loss, thrombocytopenia and other complications. The mechanism of action of these autoantibodies has not been well defined. It is clear that most aPL bind to a cryptic epitope on a normal plasma glycoprotein, Beta 2-glycoprotein I, when this glycoprotein is bound to phospholipid.
Our recent work has shown activation of cultured human vein endothelial cells (HUVEC) by IgG from patients with anticardiolipin antibodies (aCL). Incubation with aCL IgG produced a 7-fold increase in monocyte adhesion compared with incubation with IgG from normal controls. Immunofluorescent microscopy demonstrated increased expression of cell adhesion molecules including E selectin, VCAM-1, and I CAM - 1.
We have also investigated possible contributors to aPL risk, or "second hit" factors. We have identified presence of IgG2 subclass of aCL to be associated with clinical risk of thrombosis. Presence of factor V Leiden is more common in aCL patients with as compared to without thrombosis. Finally, we continue to investigate other potential genetic or environmental risk factors, including FcRIIa allelic variation and homcysteinemia.
The safety of exogenous estrogens in systemic lupus has been widely questioned, with several case reports and one retrospective study suggesting an increased risk of flare associated with oral contraceptive use. Because of the potential benefits of oral contraceptives and hormone replacement therapy, we are conducting a nationwide multicenter randomized placebo-controlled double blind study to evaluate the safety of these preparations in patients with stable or inactive SLE. Hospital for Special Surgery is one of 5 centers participating in this NIH funded project, which may change practice patterns if safety of estrogens is shown.
Simantov R, LaSala J, Lo SK, Gharavi AE, Sammaritano LR, Salmon JE, Silverstein RL. Activation of cultured vascular endothelial cells by antiphospholipid antibodies. J Clin Invest 96: 2211-2219, 1995.
Buyon JP, Kalunian K, Skovron ML, Petri M, Lahita R, Merrill J, Sammaritano LR, Yung C, Licciardi F, Belmont HM, Hahn B. Can women with SLE safely use exogenous estrogens? J Clin Rheum 1: 205-212, 1995.
Buyon JP, Petri MA, Kim MY, Kalunian KC, Grossman J, Hahn BH, Merrill JT, Sammaritano L, Lockshin M, Alarcon GS, Manzi S, Belmont HM, Askanase AD, Sigler L, Dooley MA, Von Feldt J, McCune WJ, Friedman A, Wachs J, Cronin M, Hearth-Holmes M, Tan M, Licciardi F. (2005) The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med. Jun 21;142(12 Pt 1):953-62.
Roman MJ, Devereux RB, Schwartz JE, Lockshin MD, Paget SA, Davis A, Crow MK, Sammaritano L, Levine DM, Shankar BA, Moeller E, Salmon JE. (2005) Arterial stiffness in chronic inflammatory diseases. Hypertension. Jul;46(1):194-9.
Ruiz-Irastorza G, Khamashta MA, Gordon C, Lockshin MD, Johns KR, Sammaritano L, Hughes GR. (2004) Measuring systemic lupus erythematosus activity during pregnancy: validation of the lupus activity index in pregnancy scale. Arthritis Rheum. Feb 15;51(1):78-82.
Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R, Crow MK, Schwartz JE, Paget SA, Devereux RB, Salmon JE. (2003) Prevalence and correlates of accelerated atherosclerosis in SLE. : N Engl J Med. Dec 18;349(25):2399-406.
Ross G, Sammaritano L, Nass R, Lockshin M. (2003) Effects of mothers' autoimmune disease during pregnancy on learning disabilities and hand preference in their children. Arch Pediatr Adolesc Med. Apr;157(4):397-402.
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