Clinical Significance of an Alloantibody against the Kell Blood Group Glycoprotein

Abstract

Background: Kell null (K₀) individuals can produce anti-Ku, an antibody against many epitopes in the Kell glycoprotein, after transfusion and/or pregnancy. Since sensitized K₀ patients are rare, little is known about anti-Ku clinical relevance and in particular about its association to hemolytic disease of the fetus and newborn. Case Report: This work describes a case of neonatal hyperbilirubinemia due to immune-mediated erythrocyte destruction by an alloantibody directed against the Kell glycoprotein. Serologic and molecular approaches identified an anti-Ku alloantibody in maternal serum. A homozygous IVS3 + 1g>a point mutation (KEL*02N.06 allele) was found to be responsible for the lack of Kell antigen expression in the mother's red blood cell and subsequent alloimmunization after a previous pregnancy. Even though in most cases Kell antibodies are clinically severe and may cause suppression of erythropoiesis, in our case the newborn had a moderate anemia and hyperbilirubinemia that was successfully treated with phototherapy without requiring exchange transfusion. Serological and molecular studies performed in the proband's family members allowed us to provide them with proper counseling regarding alloimmunization after transfusion and/or pregnancy. Conclusions: This case enlarges the understanding of the clinical significance of alloantibodies against Kell blood group antigens.

Anemia hemolítica del recién nacido secundaria a incompatibilidad del subgrupo Kell

“…Por lo general se manifiesta con anemia y no con hiperbilirrubinemia, en este caso se presentaron ambas; en comparación con casos de anemia hemolítica causados por anti-D u otros tupos o por el Rh. 12 Por la considerable hiperbilirrubinemia en las primeras horas de vida, la anemia y la prematurez se decidió realizar la exanguinotransfusión, que no es lo más común en cuanto al manejo de estos casos; ya que en los casos reportados el tratamiento responde solamente a la vigilancia del recién nacido y al uso de fototerapia. La evolución clínica del recién nacido en la unidad de cuidados intensivos neonatales fue muy buena, se realizó ultrasonido transfontanelar, el cual se reportó normal, ecocardiograma de control normal, cardiovascular sin alteraciones, se inició la vía oral por sonda orogástrica, la cual se fue incrementando con buena tolerancia hasta succionar adecuadamente a libre demanda.…”

“…Se realizaron estudios inmunohematológicos a los padres, quienes reportan incompatibilidad al antígeno Kell. Cuando existe incompatibilidad al subgrupo Kell, la principal manifestación es una anemia severa, y menos frecuente la hiperbilirrubinemia en comparación con incompatibilidad al Rh o a otros tipos de incompatibilidad anti-D. 12 Si existe una isoinmunización importante durante el embarazo y no se da un tratamiento adecuado se presenta anemia fetal progresiva, hidrops fetal, asfixia y muerte perinatal. Después del nacimiento la hiperbilirrubinemia puede progresar a kernicterus y causar daño neurológico, problemas de audición y en el desarrollo psicomotor.…”

Haemolytic of Newborn Disease-Related Red Blood Cell Alloantibodies

“…Alloimmunisation of Kell antibodies can be predicted according to the titre of amniotic bilirubin level, as the production of Kell antigen is well expressed in the early stage of erythropoiesis in the bone marrow (46). This could result in hyperbilirubinemia in neonates, which increases progressively on the 3 rd day of life, thus haemoglobin and haematocrit levels will drop and result in moderate anaemia (47).…”

Generation of ‘designer erythroblasts’ lacking one or more blood group systems from CRISPR/Cas9 gene‐edited human‐induced pluripotent stem cells

“…At times, alloantibodies are directed against a high‐prevalence antigen (present on RBCs of >99% population) for instance, anti‐Rh17: directed against the Rh17 antigen of the Rh blood group system, 4 anti‐U: directed against the U antigen residing on Glycophorin B (GPB) of the MNS blood group system, 5 , 6 or anti‐Ku directed against Kell glycoprotein of the Kell blood group system. 7 Serologic testing of alloantibodies against high‐prevalence antigens is difficult because they give a positive reaction with all cells in the panel. 8 To confirm the specificity of such alloantibodies, diagnostic laboratories require antigen‐negative reagent RBCs like Rh null, GPB null or Kx null/Kell low.…”