title: Gestation age dependent transfer of human immunoglobulins across placenta in timed-pregnant guinea pigs.
abstract: BACKGROUND
  When administered during pregnancy, antibodies and other biologic drugs that contain the Fc part of the IgG molecule can traverse the placenta. Although it is generally accepted that the FcRn receptor mediates this process, gaps remain in our understanding of underlying details in humans and in common laboratory animal species.
  
  
  METHODS
  We expanded our previous studies in timed-pregnant guinea pigs to both measure the transport of human (h) IgG at earlier gestation ages in vivo and evaluate FcRn function in vitro using Surface Plasmon Resonance (SPR) and Madin-Darby canine kidney cells (MDCK) that express guinea pig (gp) FcRn.
  
  
  RESULTS
  In timed-pregnant guinea pigs both the average concentration of hIgG in the fetus and its ratio to maternal hIgG concentration increase exponentially with gestation age. Thus, hIgG fetal:maternal concentration ratios increase from an average of 1% to 3%, 17%, and 76% on GD ∼26, 35, 46, and 54, respectively. In vitro, gpFcRn immobilized on a solid surface can bind hIgG and gpIgG preparations in a similar manner. All engineered human Fc isotype-specific constructs were internalized by MDCK-gpFcRn cells at significant levels. While not significant, their recycling and hIgG transcytosis by this cell line also trend higher than background controls.
  
  
  CONCLUSIONS
  Pregnant guinea pigs exhibit similarities with humans in the degree and timing of transplacental transfer as well as the ability of their FcRn to bind and internalize hIgG in vitro. Further studies are needed to guide building appropriate systems for the evaluation of FcRn mediated function of human immunoglobulin therapies.
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States.
authors.forename: Malgorzata G
authors.initials: MG
authors.lastname: Norton
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Stuart
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States.
authors.forename: Denise
authors.initials: D
authors.lastname: Toibero
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States.
authors.forename: Shelby
authors.initials: S
authors.lastname: Dahlen
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States.
authors.forename: Lilin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Division of Hematology Research and Review, Office of Blood Research and Review, CBER, FDA, United States. Electronic address: evi.struble@fda.hhs.gov.
authors.forename: Evi B
authors.initials: EB
authors.lastname: Struble
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D005333:Fetus / Q000378:metabolism; D005865:Gestational Age; D006168:Guinea Pigs; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D021381:Protein Transport / Q000502:physiology
chemical_list: D007136:Immunoglobulins
keywords: Transplacental immunoglobulin transfer