A Possible Coagulation‐Independent Mechanism for Pregnancy Loss Involving β₂glycoprotein 1‐Dependent Antiphospholipid Antibodies and CD1d

Abstract

PROBLEM β(2) glycoprotein1 (β(2) GP1)-dependent antiphospholipid antibodies (aPL) increase the risk for recurrent pregnancy loss. We address whether anti-β(2) GP1 antibodies can interact with phosphatidylserine (PS)-bearing CD1d on trophoblast cells and induce local inflammation. METHODS CD1d-bearing choriocarcinoma cells were used in flow cytometry and immunoprecipitation experiments. CD1d-mediated cytokine induction was assessed using antibody cross-linking. Cytokine production during co-culture of decidual lymphocytes with CD1d-bearing cells was also examined. RESULTS Trophoblast surface-expressed CD1d forms a complex with PS-bound β(2) GP1. Anti-β(2) GP1 mAb cross-linking causes IL12p70 release from CD1d-bearing cells. IL12p70 release from CD1d-bearing trophoblast cells was also induced during co-culture with human decidual lymphocytes. The addition of anti-β2GP1 mAb to co-cultures resulted in a three-fold increase in IL12p70 secretion. IFNγ secretion from decidual lymphocytes was also induced during co-culture with anti-β2GP1 mAbs. CONCLUSIONS β(2) GP1-dependent IL12 release from CD1d-bearing trophoblast in the presence of aPL may link the antiphospholipid syndrome to pregnancy loss via an inflammatory mechanism.

Complementemia in pregnancies with antiphospholipid syndrome

“…Anti-β2GPI antibodies have been shown to interact with the PS-bearing CD1d, causing release of IL12 and induction of IFNα production, thus supplying additional evidence that APS-related pregnancy loss involves an inflammatory mechanism. 41…”

“…Anti-b2GPI antibodies have been shown to interact with the PS-bearing CD1d, causing release of IL12 and induction of IFNa production, thus supplying additional evidence that APS-related pregnancy loss involves an inflammatory mechanism. 41 Recently, the role of anti-C1q antibodies in complement activation has been investigated both in APS patients and in unexplained recurrent pregnancy loss. Oku et al 42 firstly highlighted the association of anti-C1q antibodies with complement activation in 40 consecutive primary APS.…”

Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFα expression in Sprague-Dawley rats

“…Invariant NKT cells are innate T lymphocytes that respond rapidly to glycolipid antigens by secreting copious amounts of Th1, Th2, and Th17 cytokines in response to glycolipids presented by the CD1d molecule on antigen presenting cells (Bendelac et al, 2007, Kronenberg andGapin, 2002). Human decidua contains villous and extravillous trophoblasts that express CD1d, which mediates antigen presentation to iNKT cells (Iwasawa et al, 2012, Jenkinson et al, 1999, Matsumoto et al, 2008, Uemura et al, 2008. Activated decidual iNKT cells secrete IFNγ and GM-CSF, whereas peripheral blood iNKT cells exhibit a Th2 cytokine bias of IL-4 production during pregnancy (Boyson et al, 2002).…”

Assessment of Maternity Staff Nurses Knowledge Regarding Antiphospholipid syndrome

“…APS make unusual proteins called antiphospholipid autoantibodies in the blood. This makes blood stream flow dishonorably can lead to dangerous clotting in arteries and veins thrombosis that result in various problem for pregnant woman as sever preeclampsia miscarriage , still birth , preterm labor (Iwasawa , et al, 2011 andDennen &Gabrielle , (2013).…”