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Anti-phospholipid induced murine fetal loss: novel protective effect of a peptide targeting the β2 glycoprotein I phospholipid-binding site. Implications for human fetal loss.
- Source :
-
Journal of autoimmunity [J Autoimmun] 2012 May; Vol. 38 (2-3), pp. J209-15. Date of Electronic Publication: 2011 Dec 22. - Publication Year :
- 2012
-
Abstract
- β2 glycoprotein I (β2GPI)-dependent anti-phospholipid antibodies (aPL) induce thrombosis and affect pregnancy. The CMV-derived synthetic peptide TIFI mimics the PL-binding site of β2GPI and inhibits β2GPI cell-binding in vitro and aPL-mediated thrombosis in vivo. Here we investigated the effect of TIFI on aPL-induced fetal loss in mice. TIFI inhibitory effect on in vitro aPL binding to human trophoblasts was evaluated by indirect immunofluorescence and ELISA. TIFI effect on aPL-induced fetal loss was investigated in pregnant C57BL/6 mice treated with aPL or normal IgG (NHS). Placenta/fetus weight and histology and RNA expression were analyzed. TIFI, but not the control peptide VITT, displayed a dose-dependent inhibition of aPL binding to trophoblasts in vitro. Injection of low doses of aPL at day 0 of pregnancy caused growth retardation and increased fetal loss rate, both significantly reduced by TIFI but not VITT. Consistent with observations in humans, histological analysis showed no evidence of inflammation in this model, as confirmed by the absence of an inflammatory signature in gene expression analysis, which in turn revealed a TIFI-dependent modulation of molecules involved in differentiation and development processes. These findings support the non-inflammatory pathogenic role of aPL and suggest innovative therapeutic approaches to aPL-dependent fetal loss.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Abortion, Spontaneous prevention & control
Animals
Antibodies, Antiphospholipid metabolism
Binding Sites
Female
Gene Expression Profiling
Humans
Mice
Mice, Inbred C57BL
Peptides administration & dosage
Peptides pharmacology
Placenta metabolism
Placenta pathology
Pregnancy
Protein Binding
Trophoblasts drug effects
Trophoblasts metabolism
Abortion, Spontaneous immunology
Antibodies, Antiphospholipid immunology
Peptides metabolism
beta 2-Glycoprotein I chemistry
beta 2-Glycoprotein I metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9157
- Volume :
- 38
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- Journal of autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 22196923
- Full Text :
- https://doi.org/10.1016/j.jaut.2011.11.009