Anti-phospholipid induced murine fetal loss: Novel protective effect of a peptide targeting the beta 2 glycoprotein I phospholipid-binding site. Implications for human fetal loss

作者：de la Torre Yeny Martinez; Pregnolato Francesca; D' Amelio Fabio; Grossi Claudia; Di Simone Nicoletta; Pasqualini Fabio; Nebuloni Manuela; Chen Pojen; Pierangeli Silvia; Bassani Niccolo; Ambrogi Federico; Borghi Maria Orietta; Vecchi Annunciata; Locati Massimo; Meroni Pier Luigi^*

来源：Journal of Autoimmunity, 2012, 38(2-3): J209-J215.

DOI：10.1016/j.jaut.2011.11.009

• Anti-phospholipid syndrome
• Pregnancy complications
• beta 2 glycoprotein I
• Murine models
• TIFI

beta 2 glycoprotein I (beta 2GPI)-dependent anti-phospholipid antibodies (aPL) induce thrombosis and affect pregnancy. The CMV-derived synthetic peptide TIFI mimics the PL-binding site of beta 2GPI and inhibits beta 2GPI 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.

• 出版日期2012-5