title: Multiple injections of anti-mouse β2glycoprotein 1 antibody induce FcRγ-dependent fetal growth restriction (FGR) in mice.
abstract: OBJECTIVE
  The antiphospholipid syndrome (APS) is characterized by the presence of circulating antiphospholipid 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-β2 glycoprotein I (aβ2GPI) antibody is one of the aPLs and considered to be a specific and important marker for APS. However, pathophysiological changes induced by aβ2GPI antibodies in FGR are largely unknown.
  
  
  METHODS
  In the present study, we developed a murine FGR model induced by multiple injections of WBCAL-1, a well-characterized mouse aβ2GPI monoclonal antibody.
  
  
  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, FcRγ deficiency protected the fetuses from aβ2GPI antibody-induced injuries.
  
  
  CONCLUSIONS
  Our present findings suggest that proteinuria is a symptom associated with APS-related FGR with placental and renal tissue injuries, and that FcRγ might be a molecular target for prevention of aβ2GPI antibody-mediated obstetrical pathologies.
authors.affiliation: Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan. kawaguchi-rie@jikei.ac.jp
authors.forename: R
authors.initials: R
authors.lastname: Kawaguchi
authors.forename: S
authors.initials: S
authors.lastname: Nunomura
authors.forename: N
authors.initials: N
authors.lastname: Umehara
authors.forename: T
authors.initials: T
authors.lastname: Nikaido
authors.forename: B
authors.initials: B
authors.lastname: Huppertz
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: C
authors.initials: C
authors.lastname: Ra
mesh_terms: D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000652:urine; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000276:immunology* / Q000517:prevention & control / Q000652:urine; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D008854:Microscopy, Electron; D010920:Placenta / Q000276:immunology / Q000473:pathology; D011247:Pregnancy; D011507:Proteinuria; D017452:Receptors, IgG / Q000172:deficiency / Q000502:physiology*; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D017452:Receptors, IgG; D053482:beta 2-Glycoprotein I