PMID- 19079257
OWN - NLM
STAT- MEDLINE
DCOM- 20090204
LR  - 20211020
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 15
IP  - 1
DP  - 2009 Jan
TI  - Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in 
      maternal lupus.
PG  - 91-6
LID - 10.1038/nm.1892 [doi]
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by 
      autoantibodies and preferentially affecting women of childbearing age. Because 
      the offspring of mothers with SLE show a high frequency of learning disorders, we 
      hypothesized that maternally transferred autoantibodies that bind DNA and the 
      N-methyl-D-aspartate receptor (NMDAR) could have a pathogenic role during fetal 
      brain development. Here we describe a maternal SLE mouse model wherein pregnant 
      dams harbored DNA-specific, NMDAR-specific autoantibodies throughout gestation. 
      High titers of these autoantibodies in maternal circulation led to histological 
      abnormalities in fetal brain and subsequent cognitive impairments in adult 
      offspring. These data support a paradigm in which in utero exposure to neurotoxic 
      autoantibodies causes abnormal brain development with long-term consequences. 
      This paradigm may apply to multiple congenital neuropsychiatric disorders.
FAU - Lee, Ji Y
AU  - Lee JY
AD  - Albert Einstein College of Medicine, Department of Microbiology & Immunology, 
      Bronx, NY 10461, USA.
FAU - Huerta, Patricio T
AU  - Huerta PT
FAU - Zhang, Jie
AU  - Zhang J
FAU - Kowal, Czeslawa
AU  - Kowal C
FAU - Bertini, Eva
AU  - Bertini E
FAU - Volpe, Bruce T
AU  - Volpe BT
FAU - Diamond, Betty
AU  - Diamond B
LA  - eng
GR  - P01 AI073693/AI/NIAID NIH HHS/United States
GR  - P01 AI073693-01A10004/AI/NIAID NIH HHS/United States
GR  - R01 AR049126/AR/NIAMS NIH HHS/United States
GR  - R01 AR049126-06/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081214
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Autoantibodies)
RN  - 0 (Cytotoxins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Animals
MH  - Antibodies, Antinuclear/immunology
MH  - Autoantibodies/blood/*immunology
MH  - Cytotoxins/immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Lupus Erythematosus, Systemic/blood/complications/*immunology
MH  - Maternal-Fetal Exchange/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nervous System Malformations/*etiology/immunology
MH  - Neurons/*immunology/metabolism
MH  - Pregnancy
MH  - Pregnancy Complications/blood/*immunology
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
PMC - PMC2615794
MID - NIHMS76032
EDAT- 2008/12/17 09:00
MHDA- 2009/02/05 09:00
PMCR- 2009/07/01
CRDT- 2008/12/17 09:00
PHST- 2008/04/23 00:00 [received]
PHST- 2008/10/27 00:00 [accepted]
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/02/05 09:00 [medline]
PHST- 2009/07/01 00:00 [pmc-release]
AID - nm.1892 [pii]
AID - 10.1038/nm.1892 [doi]
PST - ppublish
SO  - Nat Med. 2009 Jan;15(1):91-6. doi: 10.1038/nm.1892. Epub 2008 Dec 14.