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a Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Rome, Italy b Allergy, Clinical Immunology & Rheumatology Unit, IRCCS Istituto Auxologico Italiano, University of Milan, Milan, Italy c Department of Internal Medicine, University of Milan, Milan, Italy
Key Words: beta-2 glycoprotein I • antiphospholipid antibodies • trophoblast • fetal loss • apoptosis
Address for correspondence: Pier Luigi Meroni, M.D., Allergy, Clinical Immunology & Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Via G. Spagnoletto, 3, 20149 Milan, Italy. Voice: +39-02-61911-2553; fax: +39-02-61911-2559. e-mail: pierluigi.meroni{at}unimi.it
Antiphospholipid antibodies (aPLs) reacting with beta-2 glycoprotein I (
 2GPI) have been associated with recurrent fetal loss and pregnancy complications. The aim of the study was to investigate whether aPLs with anti-2GPI specificity induce apoptosis of human trophoblasts in vitro. To this end, human anti-2GPI monoclonal IgM derived from a patient with antiphospholipid syndrome and a human irrelevant monoclonal IgM were incubated with human trophoblast cell cultures for 24, 48, and 72 h. In all the cultures we evaluated: (i) Bcl-2 and Bax mRNA and protein expression by Western blot and reverse transcription polymerase chain reaction (RT-PCR), respectively; (ii) DNA fragmentation by a commercial ELISA kit and by agarose gel electrophoresis; and (iii) the percentage of cells reactive with the monoclonal antibody (MAb) M30 by indirect immunofluorescence. The results were: Bcl-2/Bax ratio increased in untreated trophoblast cells during the time of culture, showing the highest values detectable after 72 h (2.68 and 2.28 at protein and mRNA levels, respectively). Cell incubation with anti-2GPI MAbs induced a significant Bcl-2/Bax ratio reduction in comparison with untreated cells (1.22 and 1.28 at protein and mRNA levels, respectively, after 72 h incubation). No significant difference was detected after cell exposure to irrelevant MAbs. However, neither DNA fragmentation nor increase in cells positive for the caspase-cleaved epitope of cytokeratin 18 cytoskeletal protein (M30) was found. In Conclusion, anti-2GPI antibodies react with trophoblast cells and reduce the Bcl-2/Bax ratio, but without any clear apoptotic effect.
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