Multiple injections of anti-mouse beta 2glycoprotein 1 antibody induce FcR gamma-dependent fetal growth restriction (FGR) in mice

作者：Kawaguchi R^*; Nunomura S; Umehara N; Nikaido T; Huppertz B; Tanaka T; Ra C

来源：Placenta, 2012, 33(7): 540-547.

DOI：10.1016/j.placenta.2012.03.010

• Antiphospholipid antibody syndrome (APS)
• Fetal growth restriction (FGR)
• Mouse model
• Anti-beta 2 glycoprotein I (beta 2GPI) antibody
• FcR gamma deficient mice

Objectives: The antiphospholipid syndrome (APS) is characterized by the presence of circulating anti-phospholipid antibodies (aPLs), is a leading cause for thromboembolic events, repeated miscarriage, fetal loss and is a major risk factor for fetal growth restriction (FGR) and preeclampsia. In human, anti-beta 2 glycoprotein I (a beta 2GPI) antibody is one of the aPLs and considered to be a specific and important marker for APS. However, pathophysiological changes induced by a beta 2GPI antibodies in FGR are largely unknown. %26lt;br%26gt;Methods: In the present study, we developed a murine FGR model induced by multiple injections of WBCAL-1, a well-characterized mouse a beta 2GPI monoclonal antibody. %26lt;br%26gt;Results: Administration of WBCAL-1, but not the isotype control antibody and saline, into pregnant mice specifically decreased the size of fetuses and placentas without affecting the number of delivered pups. Also, a significant increase in urinary albumin and electron microscopic changes, such as splitting layers of basal membranes in the placental labyrinth and rearrangement of pores in glomerular endothelial cells, were observed in WBCAL-1 treated mice. WBCAL-1 injection did not induce any changes in blood pressure and typical parameters of blood thromboembolic symptoms. Furthermore, FcR gamma deficiency protected the fetuses from a beta 2GPI antibody-induced injuries. %26lt;br%26gt;Conclusions: Our present findings suggest that proteinuria is a symptom associated with APS-related FGR with placental and renal tissue injuries, and that FcR gamma might be a molecular target for prevention of a beta 2GPI antibody-mediated obstetrical pathologies.

• 出版日期2012-7