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Updated: Aug 7, 2025
Isolation of Leukocytes from the Murine Tissues at the Maternal-Fetal Interface
Published on: May 21, 2015
Fetal Alloimmune Hemolytic Anemia (AHA) as a Potential Target for Transamniotic Fetal Immunotherapy (TRAFIT)
Ashlyn E Whitlock1, Kamila Moskowitzova1, Ina Kycia1
1Departments of Surgery, Boston Children's Hospital & Harvard Medical School, Boston, MA, USA.
Purpose:
Fetal alloimmune hemolytic anemia (AHA) resulting from maternal antibodies against fetal erythrocytes may require fetal administration of immunoglobulin-G (IgG) via invasive methods. IgG can reach the fetal circulation after transamniotic fetal immunotherapy (TRAFIT). We sought to both develop a model of AHA and to test TRAFIT as a potential treatment.
Methods:
Sprague-Dawley fetuses (n = 113) received intra-amniotic injections on gestational-day 18 (E18, term = E21) of either saline (control; n = 40), anti-rat-erythrocyte antibodies (AHA; n = 37), or anti-rat-erythrocyte antibodies plus IgG (AHA + IgG; n = 36). At term, blood was procured for red blood count (RBC), hematocrit, or ELISA for inflammatory markers.
Results:
There was no difference in survival [95% (107/113)] across groups (p = 0.87). Both hematocrit and RBC were significantly lower in the AHA group than controls (p < 0.001). Although still significantly lower than controls (p < 0.001), both hematocrit and RBC significantly increased in AHA + IgG group compared to AHA alone (p < 0.001). Pro-inflammatory TNF-α and IL1-β were significantly elevated from controls in the AHA group, but not in AHA + IgG (p < 0.001-0.159).
Conclusions:
Intra-amniotic injection of anti-rat-erythrocyte antibodies can reproduce manifestations of fetal AHA, constituting a practical model of this disease. Transamniotic fetal immunotherapy with IgG reduces anemia in this model and may emerge as a new minimally invasive means of treatment.
Type Of Study:
Animal and laboratory study.
Level Of Evidence:
N/A (animal and laboratory study).
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