Problem: A threefold higher prevalence of antinuclear antibodies (ANA) has been reported in patients with recurrent pregnancy loss (RPL). Nevertheless, the role of ANA in reproductive failure is still unclear. The aim of this study was to investigate the role of ANA during early pregnancy in vivo. Method of study: We used pregnant mice treated with immunoglobulin G (IgG) obtained from normal healthy subjects (NHS); ANA+ sera of patients with RPL; and ANA+ sera from women with uncomplicated pregnancies (HW). Placental immunohistochemical/immunofluorescence staining was performed to detect complement and immune complex deposition. ELISA was performed to evaluate complement levels. Results: ANA+ IgG from RPL women significantly increased embryo resorption rate, reduced C3, and increased C3a serum levels compared to NHS IgG or ANA+-HW IgG. Increased C3 deposition and increased immune complex staining in placental tissues from mice treated with ANA+-RPL IgG fraction compared to NHS- and ANA+-HW-IgG-treated mice were found. Conclusion: ANA+ IgG injection in mice is able to induce fetal resorption and complement activation. The presence on placental tissues of immune complexes and complement fragments suggests the complement activation as a possible mechanism of placental damage. Copyright
Veglia, M., D'Ippolito, S., Marana, R., Di Nicuolo, F., Castellani, R., Bruno, V., Fiorelli, A., Ria, F., Maulucci, G., De Spirito, M., Migliara, G., Scambia, G., Di Simone, N., Human IgG Antinuclear Antibodies Induce Pregnancy Loss in Mice by Increasing Immune Complex Deposition in Placental Tissue: In Vivo Study, <<AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY>>, 2015; 74 (6): 542-552. [doi:10.1111/aji.12429] [http://hdl.handle.net/10807/117599]
Human IgG Antinuclear Antibodies Induce Pregnancy Loss in Mice by Increasing Immune Complex Deposition in Placental Tissue: In Vivo Study
Veglia, Manuela;D'Ippolito, Silvia;Marana, Riccardo;Di Nicuolo, Fiorella;Castellani, Roberta;Ria, Francesco;Maulucci, Giuseppe;De Spirito, Marco;Migliara, Giuseppe;Scambia, Giovanni;Di Simone, Nicoletta
2015
Abstract
Problem: A threefold higher prevalence of antinuclear antibodies (ANA) has been reported in patients with recurrent pregnancy loss (RPL). Nevertheless, the role of ANA in reproductive failure is still unclear. The aim of this study was to investigate the role of ANA during early pregnancy in vivo. Method of study: We used pregnant mice treated with immunoglobulin G (IgG) obtained from normal healthy subjects (NHS); ANA+ sera of patients with RPL; and ANA+ sera from women with uncomplicated pregnancies (HW). Placental immunohistochemical/immunofluorescence staining was performed to detect complement and immune complex deposition. ELISA was performed to evaluate complement levels. Results: ANA+ IgG from RPL women significantly increased embryo resorption rate, reduced C3, and increased C3a serum levels compared to NHS IgG or ANA+-HW IgG. Increased C3 deposition and increased immune complex staining in placental tissues from mice treated with ANA+-RPL IgG fraction compared to NHS- and ANA+-HW-IgG-treated mice were found. Conclusion: ANA+ IgG injection in mice is able to induce fetal resorption and complement activation. The presence on placental tissues of immune complexes and complement fragments suggests the complement activation as a possible mechanism of placental damage. Copyright
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