[show abstract][hide abstract] ABSTRACT: Maternal antibodies transported across the placenta protect the newborn. Maternal immunoglobulin G (IgG) concentrations in fetal blood increase from early in the second trimester through term, most antibodies being acquired during the third trimester. IgG1 is the most efficiently transported subclass and IgG2 the least. Transfer across the syncytiotrophoblast of the chorionic villi is mediated by the neonatal Fc receptor, FcRn. Immune complexes are absorbed in the stroma of the villi, probably by FcgammaRI, FcgammaRII, and FcgammaRIII on placental macrophages. The mechanism of IgG transport across the endothelium of fetal capillaries is not understood. Endothelial cells in terminal villi express FcgammaRIIb. However, it is not known whether this receptor transports IgG or prevents transport of immune complexes to the fetus.
[show abstract][hide abstract] ABSTRACT: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal stem cell disorder, which affects women of child-bearing age. PNH is associated with thrombotic complications, which are the main causes of morbidity and mortality. Management of a pregnant woman with PNH remains a challenge due to high incidence of thrombotic complications and the difficulty of differentiating a PNH crisis from the complications of pregnancy. PNH is associated with an increased rate of premature labor and fetal loss. Eculizumab, a humanized monoclonal antibody directed against the terminal complement protein C5, has revolutionized treatment of PNH. However, the role of eculizumab in pregnancy is unclear. We review the current strategies for the management of pregnant women with PNH, underline the controversies and present our recommendations.
Leukemia research 11/2009; 34(5):566-71. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: We tested the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation, in patients with paroxysmal nocturnal hemoglobinuria (PNH).
We conducted a double-blind, randomized, placebo-controlled, multicenter, phase 3 trial. Patients received either placebo or eculizumab intravenously; eculizumab was given at a dose of 600 mg weekly for 4 weeks, followed 1 week later by a 900-mg dose and then 900 mg every other week through week 26. The two primary end points were the stabilization of hemoglobin levels and the number of units of packed red cells transfused. Biochemical indicators of intravascular hemolysis and the patients' quality of life were also assessed.
Eighty-seven patients underwent randomization. Stabilization of hemoglobin levels in the absence of transfusions was achieved in 49% (21 of 43) of the patients assigned to eculizumab and none (0 of 44) of those assigned to placebo (P<0.001). During the study, a median of 0 units of packed red cells was administered in the eculizumab group, as compared with 10 units in the placebo group (P<0.001). Eculizumab reduced intravascular hemolysis, as shown by the 85.8% lower median area under the curve for lactate dehydrogenase plotted against time (in days) in the eculizumab group, as compared with the placebo group (58,587 vs. 411,822 U per liter; P<0.001). Clinically significant improvements were also found in the quality of life, as measured by scores on the Functional Assessment of Chronic Illness Therapy-Fatigue instrument (P<0.001) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Of the 87 patients, 4 in the eculizumab group and 9 in the placebo group had serious adverse events, none of which were considered to be treatment-related; all these patients recovered without sequelae.
Eculizumab is an effective therapy for PNH.
New England Journal of Medicine 10/2006; 355(12):1233-43. · 51.66 Impact Factor
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