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VIDEO: Murine Model for Hemolytic Disease of the Fetus and Newborn

Reported in the journal Blood, researchers have developed the first-ever animal model of HDFN.

HDFN is a condition whereby IgG alloantibodies cross the placenta and attack red blood cells in the fetal circulation.

Here is Dr. Jeanne Hendrickson, who co-authored the recent study:

“HDFN affects approximately 6 in every 1000 live births, with antigens in the KEL and Rh systems being known to cause particularly severe disease. Other than transfusion or pregnancy avoidance, there are no known therapies to prevent alloimmunization to any antigen outside of RhD. Furthermore, there are no targeted therapies available for women who enter pregnancy already alloimmunized.“

Although the condition was first recognized over 400 years ago, the mechanisms through which HDFN occurs and can be treated are not fully understood.

Dr. Leslie Silberstein co-authored an editorial accompanying the current study, and noted:

“We still have very little understanding about the mechanism by which an antibody that is formed in the mother passes through the placenta and is able to recognize and destroy the fetal red blood cells which consequently can cause anemia but also a severe erythroblastosis fetalis, and it turns out that the basis by which polyclonal RH immunoglobulin in fact works it’s still largely an enigma.”

Dr. Hendrickson and her research team were able to develop a pregnancy-associated murine model with red blood cell-specific expression of the human KEL antigen:

“Females lacking the human KEL antigen on their red cells bred with males expressing this antigen develop anti-KEL glycoprotein alloantibodies in response to fetal/maternal bleeds. These maternal anti-KEL alloantibodies then cross the placenta, bind to fetal red cells and red cell precursors expressing the KEL antigen, and lead to fetal anemia or even hydrops fetalis and intrauterine fetal demise.”

It is expected that this new model of HDFN will help in the development of further preventative or therapeutic options.

Here is Dr. Hendrickson:

“It is my hope that this model will ultimately allow for the development of translatable, targeted maternal immunomodulatory therapies, to prevent alloantibody development altogether or to mitigate the dangers of existing maternal alloantibodies to developing fetuses.”

We’ll be back on October 15th with another edition of Transfusion News. Thanks for joining us.

References

1.    Stowell SR, Henry KL, Smith NH, Hudson KE, Halverson GR, Park JC, Bennett AM, Girard-Pierce KR, Arthur CM, Bunting ST, Zimring JC, Hendrickson JE. Alloantibodies to a paternally derived RBC KEL antigen lead to hemolytic disease of the fetus/newborn in a murine model. Blood 2013;122: 1494-504.

2.   Luckey CJ, Silberstein LE. A mouse model of hemolytic disease of the newborn. Blood 2013;122: 1334-5.

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