Reduced placental growth and hCG secretion in vitro induced by antiphospholipid antibodies but not by anti-Ro or anti-La: studies on sera from women with SLE/PAPS

Abstract

Systemic lupus erythematosus (SLE) and primary anti-phospholipid syndrome (PAPS) are autoimmune diseases causing recurrent pregnancy loss. We hypothesized that anti-phospholipid antibodies (aPL), but not anti-Ro and anti-La antibodies, might have a role through direct placental damage. We cultured human placental explants in sera from women with SLE/PAPS with different antibodies. These sera were found to reduce placental growth and increase trophoblastic apoptosis. No effect was found on estradiol or progesterone secretion, but inhibition in betahCG secretion was detected. BetahCG was reduced in women with a history of recurrent pregnancy loss or thromboembolic events, and was also the most sensitive marker when examining the effects of specific antibodies. High titers of aPL were found to cause the largest reduction in betahCG. Anti-Ro and anti-La did not induce placental damage. A strong correlation was found between the rise in the number of different antibodies in the sera and the incidence of recurrent pregnancy loss, which was also accompanied by a decline in the betahCG levels. In conclusion, aPL, but not anti-Ro or anti-La, may cause placental damage in vitro. Thus betahCG levels might constitute a predictive marker for the risk of placental damage and pregnancy loss in women with SLE/PAPS.

Prevention of complete heart block in children of mothers with anti-SSA/Ro and anti-SSB/La autoantibodies: detection and treatment of first-degree atrioventricular block

“…In general, outside of the context of heart injury, anti-SSA/Ro and anti-SSB/La exposure is not clearly associated with growth development. This observation is also supported by the lack of reduced placenta growth when exposed to anti-SSA/Ro and anti-SSB/La [12].…”

A Unique Preliminary Study on Placental Apoptosis in Mice with Passive Immunization of Anti-Phosphatidylethanolamine Antibodies and Anti-Factor XII Antibodies

“…Apoptosis in the trophoblasts was observed after passive 27–29 or active immunization in experimental animals 30–32 . Other studies also have indicated that the antibodies listed above stimulated apoptosis in human trophoblast in vitro 33–36 . In contrast, there have been no animal studies regarding aPE and anti‐FXII.…”

The role of anti-phospholipid antibodies in autoimmune reproductive failure

“…The majority of studies have examined the effects of polyclonal aPL isolated from patient sera, as well as murine monoclonal aPL on placental explants or cell lines (Yacobi et al 2002, Ornoy et al 2003, Bose et al 2004, Schwartz et al 2007. Studies examining the mechanism of reduced migration showed that aPL mediate this effect possibly through the downregulation of interleukin 6 (IL6; Mulla et al 2010) and the up-reguation of TIMP2 (Albert et al 2014), all independently of Toll-like receptor 4 (TLR4).…”

“…Several in vitro studies have reported an increase in trophoblast death in response to aPL using either term trophoblasts or first-trimester trophoblasts (Di Simone et al 2001, Yacobi et al 2002, Ornoy et al 2003, Schwartz et al 2007, Chen et al 2009, Mulla et al 2009). Cytotrophoblasts isolated from term placentae (Di Simone et al 2001 have been shown to alter their expression of the apoptotic regulators Bax and Bcl2 in response to aPL, but without overt signs of cell death (Di Simone et al 2006).…”

“…In vitro studies suggest that aPL may alter the cytokine and hormonal milieu produced by trophoblasts, leading to a pro-inflammatory environment at the maternal-placental interface and altered trophoblast function (Abrahams 2009). It was shown nearly two decades ago that aPL reduce the basal and GnRH-induced production of human chorionic gonadotropin (hCG; Katsuragawa et al 1997, Di Simone et al 2000b, Schwartz et al 2007. Recent evidence suggests that this aPL-mediated reduction in hCG secretion by trophoblasts is mediated via TLR4 (Marchetti et al 2014).…”