Female mouse fetal loss mediated by maternal autoantibody.

The Journal of Experimental Medicine
Li WangBetty Diamond

Abstract

Systemic lupus erythematosus (SLE), a disease of women during childbearing years, is characterized by the production of double-stranded DNA antibodies. A subset of these antibodies, present in 40% of patients, cross-reacts with the NR2A and NR2B subunits of the N-methyl-d-aspartate receptor (NMDAR). In this study, we show that, in mouse models, these antibodies cause a loss of female fetus viability by inducing apoptosis of NR2A-expressing neurons within the brainstem late in fetal development; gender specificity derives from a time-dependent increased expression of NR2A in female brainstem or increased vulnerability of female fetal neurons to signaling through NR2A-containing NMDARs. This paradigm is consistent with available data on the sex ratio of live births of women with SLE. It represents a novel mechanism by which maternal autoantibodies can severely affect fetal health in a gender-specific fashion and raises the question of how many maternal antibodies affect brain development or exhibit gender-specific fetal effects.

References

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Citations

Jun 6, 2012·The Journal of Experimental Medicine·Ulf Andersson, Kevin J Tracey
Mar 23, 2013·Annual Review of Immunology·B DiamondB T Volpe
Feb 5, 2013·The Journal of Rheumatology·Rachna AggarwalR Hal Scofield
Oct 10, 2012·Arthritis and Rheumatism· Michael D LockshinJane E Salmon
Jul 21, 2015·Nature Reviews. Neuroscience·Myka L Estes, A Kimberley McAllister
Oct 24, 2015·Trends in Immunology·Lior BrimbergBetty Diamond
May 10, 2016·Arthritis & Rheumatology·Évelyne VinetSasha Bernatsky
Aug 27, 2016·Arthritis & Rheumatology·Elizabeth V ArkemaJulia F Simard
Sep 7, 2018·The Journal of Experimental Medicine·Jacquelyn NestorBetty Diamond
Oct 16, 2015·Immunologic Research·Patricio T HuertaTomás S Huerta
May 23, 2012·Nature Reviews. Rheumatology·Ellen F Carney
Aug 21, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claudia RivalKenneth Tung
Sep 29, 2017·Frontiers in Immunology·Simone MaderBetty Diamond
Jun 14, 2019·Frontiers in Immunology·Adriana Gata-Garcia, Betty Diamond
Jan 6, 2019·Molecular Psychiatry·Galen MissigWilliam A Carlezon
Apr 21, 2016·Antibodies·Carolin HoffmannPilar Martinez-Martinez
Mar 31, 2021·Current Rheumatology Reports·Aida ZarfeshaniBetty Diamond
Jun 1, 2021·Journal of Neural Transmission·Niels HansenUNKNOWN + CAP (Cerebrospinal Fluid Analysis in Psychiatry)-Consortium

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Methods Mentioned

BETA
PCR
ELISA
genotyping
dissectors

Software Mentioned

AxioVision
LightCycler480

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