title: Human IgG Antinuclear Antibodies Induce Pregnancy Loss in Mice by Increasing Immune Complex Deposition in Placental Tissue: In Vivo Study.
abstract: OBJECTIVE
  A threefold higher prevalence of antinuclear antibodies (ANA) has been reported in patients with recurrent pregnancy loss (RPL). Nevertheless, the role of ANA in reproductive failure is still unclear. The aim of this study was to investigate the role of ANA during early pregnancy in vivo.
  
  
  METHODS
  We used pregnant mice treated with immunoglobulin G (IgG) obtained from normal healthy subjects (NHS); ANA(+) sera of patients with RPL; and ANA(+) sera from women with uncomplicated pregnancies (HW). Placental immunohistochemical/immunofluorescence staining was performed to detect complement and immune complex deposition. ELISA was performed to evaluate complement levels.
  
  
  RESULTS
  ANA(+) IgG from RPL women significantly increased embryo resorption rate, reduced C3, and increased C3a serum levels compared to NHS IgG or ANA(+) -HW IgG. Increased C3 deposition and increased immune complex staining in placental tissues from mice treated with ANA(+) -RPL IgG fraction compared to NHS- and ANA(+) -HW-IgG-treated mice were found.
  
  
  CONCLUSIONS
  ANA(+) IgG injection in mice is able to induce fetal resorption and complement activation. The presence on placental tissues of immune complexes and complement fragments suggests the complement activation as a possible mechanism of placental damage.
authors.affiliation: Department of Obstetrics and Gynecology, Policlinico A. Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Veglia
authors.affiliation: Department of Obstetrics and Gynecology, Policlinico A. Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: D'Ippolito
authors.affiliation: Department of Obstetrics and Gynecology, Policlinico A. Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.|International Scientific Institute Paolo VI, ISI, Università Cattolica Del Sacro Cuore, Policlinico A. Gemelli, Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Marana
authors.affiliation: Department of Obstetrics and Gynecology, Policlinico A. Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Di Nicuolo
authors.affiliation: Department of Obstetrics and Gynecology, Policlinico A. Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Castellani
authors.affiliation: Section of Gynecology and Obstetrics, Department of Surgical Sciences, Università di Tor Vergata, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bruno
authors.affiliation: Department of Obstetrics and Gynecology, Policlinico A. Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Fiorelli
authors.affiliation: Institute of General Pathology, Università Cattolica Del Sacro Cuore, Policlinico A. Gemelli, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ria
authors.affiliation: Institute of Physics, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maulucci
authors.affiliation: Institute of Physics, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Spirito
authors.affiliation: Institute of General Pathology, Università Cattolica Del Sacro Cuore, Policlinico A. Gemelli, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Migliara
authors.affiliation: Department of Obstetrics and Gynecology, Policlinico A. Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Department of Obstetrics and Gynecology, Policlinico A. Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Di Simone
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010920:Placenta / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy / Q000276:immunology; D012008:Recurrence
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D003176:Complement C3; D007074:Immunoglobulin G
keywords: Antinuclear antibodies; complement activation; recurrent pregnancy loss