PMID- 23843496
OWN - NLM
STAT- MEDLINE
DCOM- 20131107
LR  - 20210202
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 122
IP  - 7
DP  - 2013 Aug 15
TI  - Maternofetal transplacental transport of recombinant IgG antibodies lacking 
      effector functions.
PG  - 1174-81
LID - 10.1182/blood-2012-12-473843 [doi]
AB  - The neonatal Fc receptor (FcRn) directs the transfer of maternal immunoglobulin G 
      (IgG) antibodies across the placenta and thus provides the fetus and newborn with 
      passive protective humoral immunity. Pathogenic maternal IgG antibodies will also 
      be delivered via the placenta and can cause alloimmunity, which may be lethal. A 
      novel strategy to control pathogenic antibodies would be administration of a 
      nondestructive IgG antibody blocking antigen binding while retaining binding to 
      FcRn. We report on 2 human IgG3 antibodies with a hinge deletion and a C131S 
      point mutation (IgG3DeltaHinge) that eliminate complement activation and binding to 
      all classical Fcgamma receptors (FcgammaRs) and to C1q while binding to FcRn is retained. 
      Additionally, 1 of the antibodies has a single point mutation in the Fc (R435H) 
      at the binding site for FcRn (IgG3DeltaHinge:R435H). We compared transplacental 
      transport with wild-type IgG1 and IgG3, and found transport across 
      trophoblast-derived BeWo cells and ex vivo placenta perfusions with hierarchies 
      as follows: IgG3DeltaHinge:R435H>wild-type IgG1>/=IgG3DeltaHinge and 
      IgG3DeltaHinge:R435H=wild-type IgG1=wild-type IgG3>>>IgG3DeltaHinge, respectively. 
      Collectively, IgG3DeltaHinge:R435H was transported efficiently from the maternal to 
      the fetal placental compartment. Thus, IgG3DeltaHinge:R435H may be a good candidate 
      for transplacental delivery of a nondestructive antibody to the fetus to combat 
      pathogenic antibodies.
FAU - Mathiesen, Line
AU  - Mathiesen L
AD  - Department of Public Health, Faculty of Health Sciences, University of 
      Copenhagen, Copenhagen, Denmark.
FAU - Nielsen, Leif K
AU  - Nielsen LK
FAU - Andersen, Jan Terje
AU  - Andersen JT
FAU - Grevys, Algirdas
AU  - Grevys A
FAU - Sandlie, Inger
AU  - Sandlie I
FAU - Michaelsen, Terje E
AU  - Michaelsen TE
FAU - Hedegaard, Morten
AU  - Hedegaard M
FAU - Knudsen, Lisbeth E
AU  - Knudsen LE
FAU - Dziegiel, Morten Hanefeld
AU  - Dziegiel MH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130710
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Fc)
RN  - 0 (Recombinant Proteins)
RN  - TW3XAW0RCY (Fc receptor, neonatal)
SB  - IM
MH  - Antibodies/*immunology/metabolism
MH  - Binding Sites
MH  - Biological Transport
MH  - Choriocarcinoma/immunology/metabolism/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Fetus/*immunology/metabolism
MH  - Flow Cytometry
MH  - Histocompatibility Antigens Class I/*immunology/metabolism
MH  - Humans
MH  - Immunoglobulin G/*immunology/metabolism
MH  - Infant, Newborn
MH  - Maternal-Fetal Exchange/*immunology
MH  - Placenta/*immunology/metabolism
MH  - Pregnancy
MH  - Receptors, Fc/*immunology/metabolism
MH  - Recombinant Proteins/*immunology/metabolism
MH  - Uterine Neoplasms/immunology/metabolism/pathology
EDAT- 2013/07/12 06:00
MHDA- 2013/11/08 06:00
CRDT- 2013/07/12 06:00
PHST- 2013/07/12 06:00 [entrez]
PHST- 2013/07/12 06:00 [pubmed]
PHST- 2013/11/08 06:00 [medline]
AID - S0006-4971(20)54272-9 [pii]
AID - 10.1182/blood-2012-12-473843 [doi]
PST - ppublish
SO  - Blood. 2013 Aug 15;122(7):1174-81. doi: 10.1182/blood-2012-12-473843. Epub 2013 
      Jul 10.