Erythropoietic suppression in fetal anemia because of Kell alloimmunization

Vaughan, Janet; Warwick, Ruth M.; Letsky, Elizabeth A.; Nicolini, Umberto; Rodeck, Charles H.; Fisk, Nicholas M.

doi:10.1016/0002-9378(94)90477-4

Cited by 167 publications

(83 citation statements)

References 18 publications

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“…In humans, KEL is expressed on early RBC precursors with anti-KEL1 antibodies leading to in utero suppression of erythroid progenitor cells and potentially severe HDFN. 17,31 In our transgenic murine model, human KEL is expressed on murine RBC precursors as early as p.c. day 13, with anti-KEL antibodies also leading to in utero suppression of KEL erythroid progenitors.…”

Section: Discussionmentioning

confidence: 99%

Alloantibodies to a paternally derived RBC KEL antigen lead to hemolytic disease of the fetus/newborn in a murine model

Stowell

Henry

Smith

et al. 2013

Blood

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• Anti-KEL alloantibodies generated after exposure to paternally derived RBC antigens during pregnancy result in fetal anemia.• This is the first animal model of pregnancy associated HDFN, with transfusion and pregnancy resulting in boostable anti-KEL alloantibodies.Exposure to nonself red blood cell (RBC) antigens, either from transfusion or pregnancy, may result in alloimmunization and incompatible RBC clearance. First described as a pregnancy complication 80 years ago, hemolytic disease of the fetus and newborn (HDFN) is caused by alloimmunization to paternally derived RBC antigens. Despite the morbidity/mortality of HDFN, women at risk for RBC alloimmunization have few therapeutic options. Given that alloantibodies to antigens in the KEL family are among the most clinically significant, we developed a murine model with RBC-specific expression of the human KEL antigen to evaluate the impact of maternal/fetal KEL incompatibility. After exposure to fetal KEL RBCs during successive pregnancies with KEL-positive males, 21 of 21 wild-type female mice developed anti-KEL alloantibodies; intrauterine fetal anemia and/or demise occurred in a subset of KEL-positive pups born to wild type, but not agammaglobulinemic mothers. Similar to previous observations in humans, pregnancy-associated alloantibodies were detrimental in a transfusion setting, and transfusion-associated alloantibodies were detrimental in a pregnancy setting. This is the first pregnancy-associated HDFN model described to date, which will serve as a platform to develop targeted therapies to prevent and/or mitigate the dangers of RBC alloantibodies to fetuses and newborns. (Blood. 2013;122(8):1494-1504

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Section: Discussionmentioning

confidence: 99%

Alloantibodies to a paternally derived RBC KEL antigen lead to hemolytic disease of the fetus/newborn in a murine model

Stowell

Henry

Smith

et al. 2013

Blood

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“…Hemolytic disease of the newborn (HDN) due to maternal antibody to KELl is infrequent but the in cidence of anti-KELl in obstetric patients is about 0.1% [50,51], Although there is some disagreement as to the severity of anti-KELl hemolytic disease [52], mainly due to the in ability of relating antibody titers [53] or amniotic bilirubin levels [54] to HDN, maternal antibodies to KELl along with anti-D and anti-c are a significant cause of HDN [52,53,[55][56][57][58]. Recent studies suggest that, unlike anti-D [59], fetal anemia caused by KELl antibodies may involve suppression of erythropoiesis rather than hemolysis [60][61][62]. If this is the case fetal anemia, rather than HDN, may be a more appropri ate term to use when perinatal anemia is due to anti-KELl.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Molecular Basis of Kell Blood Group Phenotypes

Lee¹

1997

Vox Sanguinis

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The molecular basis of different Kell blood group phenotypes is reviewed. Sequence analysis of the Kell gene (KEL) established that single base substitutions, resulting in amino acid changes, are responsible for the different phenotypes. Most of the amino acid substitutions, with the exception of the one responsible for expression of KEL6 (Js^a), occur at the amino-terminal half of the protein, a domain that has least amino acid homology with a family of zinc endopeptidases, which include neutral endopeptidase 24.11 and endothelin-converting enzyme-1. Some of the genes were expressed in transfected cells and typed with alloantibodies to confirm that the identified mutations are responsible for antigen expression. Clinical applications of Kell blood group genotyping which include prenatal diagnosis to monitor hemolytic disease of the newborn are discussed.

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“…In this case, the fetal anaemia may have been caused by destruction of mature red cells from the fetal blood as seen in Rhesus disease or by suppression of the fetal bone marrow production as seen in Kell system allo-immunisation [2,3,4]. In both mechanisms of disease it is known that development of fetal anaemia is a gradual event giving opportunity for fetal surveillance and timely intervention.…”

Section: Discussionmentioning

confidence: 99%