Case report: HDFN caused by rare anti-LU1 alloantibodies

This case highlights the importance of considering antibodies other than anti-Rh as potential causes of HDFN.

An unusual case of hemolytic disease of the fetus and newborn (HDFN) caused by anti-LU1 (anti-Luᵃ) alloantibodies was recently published in Transfusion Medicine and Hemotherapy 

HDFN typically is a consequence of maternal alloimmunization against fetal red blood cell (RBC) antigens. RBCs exhibit many different antigens on their surface, but the ones most commonly associated with HDFN are the RH antigens.  Antibodies against the Lutheran (LU) antigen are usually considered clinically insignificant as LU antigens are expressed in placental tissue and are thought to adsorb maternal antibodies.

The case involved a 29-year-old woman  with two previous pregnancies, whose third pregnancy was complicated by fetal anemia detected at 30 weeks of gestation. 

The anemia was diagnosed through an ultrasound that revealed elevated middle cerebral artery flow velocity, and liquid accumulation in the abdomen (ascites). The physicians performed a serologic panel to rule out HDFN and detected elevated LU1 alloantibody was first identified in week 27 with a titer of 256, which rose to 1,024 by week 30. There was no history of transfusions, and previous pregnancies had been uneventful.

Cross-matching tests excluded the presence of other alloantibodies. A monocyte monolayer assay (MMA) performed at a reference laboratory revealed a monocyte index exceeding 20%, supporting the clinical relevance of the detected antibody. Given the rising antibody titers and confirmed fetal anemia,  her physicians performed an intrauterine transfusion (IUT) at 30 weeks with LU1-negative RBCs. The fetal hemoglobin levels improved quickly.

The baby was born at 37 weeks without complications. Laboratory workup at birth showed normal hemoglobin levels  and only mildly elevated bilirubin. He required no further treatments such as phototherapy. Subsequent testing confirmed the diagnosis of HDFN due to LU alloantibodies. 

The case highlights the importance of considering antibodies different to anti-Rh as potential causes of HDFN, the authors stated.

“Anti-D remains the most common cause of HDFN,” the authors wrote. “ Still, other clinical significant alloantibodies, as well as alloantibodies that normally are not clinically relevant, must also be taken into account when diagnosing fetal anemia,”

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