Kell Blood Group System
The Kell blood group system was discovered in 1946. It was named in recognition of Mrs. Kelleher, a patient whose newborn child developed hemolytic anemia due to the presence of anti-K antibodies.
Hemolytic anemia is a disorder characterized by the destruction of RBCs, leading to a lower-than-normal amount of RBCs in the body. In the case of Mrs. Kelleher, the RBCs of her infant expressed a specific antigen known as the K antigen, which was not present on her RBCs. This incompatibility in the expression of the K antigen between the maternal and neonatal blood types triggered an immune reaction and resulted in the destruction of the child’s RBCs by the anti-K antibodies in the mother’s serum.
INTRODUCTION TO KELL ANTIGENS
A total of 34 Kell antigens have been discovered so far, that are expressed in different frequencies in different populations. However, the most significant antigens of the Kell blood group system are K, k, Kpa, Kpb, Kpc, Jsa, and Jsb. Kell antigens are present on a single-pass glycophorin, called Kell glycophorin, made up of 732 amino acids. The Kell glycoprotein contains three main antigen sites:
Figure: Structure of Kell Glycoprotein
Site 1 (K/k): This is the primary and most well-known antigenic site on the Kell glycoprotein, located at amino acid 193. This site hosts two antigens: K and k (previously known as Kell and Cellano antigens, respectively). The K and k antigens differ by a point mutation, which results in a threonine (Thr) to methionine (Met) change at amino acid 193. The presence of Thr at amino acid position 193 leads to the formation of the k antigen, while the presence of Met leads to the formation of the K antigen.
The K antigen is more effective at triggering an immune reaction among all the Kell antigens. After the ABO and Rh antigens, the K antigen is the most immunogenic and one of the most clinically relevant antigens. Individuals who express the K antigen are classified as Kell-positive (K+), while those lacking the K antigen are Kell-negative (K-).
Site 2 (Kpa/Kpb/Kpc): This site, located at amino acid 281, expresses the Kpa, Kpb, and Kpc antigens. The presence of Tryptophan (Trp), Arginine (Arg), and Glutamine (Glu) at amino acid position 281 leads to the formation of Kpa, Kpb, and Kpc antigens, respectively.
Site 3 (Jsa/Jsb): This site, located at amino acid 597, expresses the Jsa and Jsb antigens. The presence of Proline (Pro) at amino acid position 597 leads to the formation of the Jsa antigen, while the presence of Leucine (Leu) leads to the formation of the Jsb antigen.
INHERITANCE OF KELL ANTIGENS
All the Kell antigens are encoded by the KEL gene located on Chromosome 7. The non-mutated or ‘normal’ form of the KEL gene codes for the high-frequency antigens k, Kpb, and Jsb on the three antigenic sites.
(Note: Humans are diploid organisms with two copies of each gene, one inherited from each parent).
A. Non-mutated KEL genes: Most individuals inherit both copies of the non-mutated form of the KEL gene (i.e. KEL/KEL) that results in the formation of all high-frequency antigens k, Kpb, and Jsb at the three antigenic sites.
B. One mutated KEL gene: Some individuals may inherit one copy of the mutated allele along with one copy of the non-mutated allele (i.e. KEL/K or KEL/Kpa or KEL/Kpc or KEL/Jsa). This will result in the formation of all the high-frequency antigens with ONE low-frequency antigen. The resulting phenotype would be one one the following, depending on which mutated allele is inherited:
k, K, Kpb, Jsb
k, Kpa, Kpb, Jsb
k, Kpb, Kpc, Jsb
k, Kpb, Jsa, Jsb
C. Two mutated KEL genes: In rare cases, an individual may inherit two copies of the mutated allele. This results in the formation of two high-frequency alleles (k, Kpb, or Jsb) and one or two low-frequency alleles (K, Kpa, Kpc, or Jsa), depending on which mutated alleles are inherited.
Ko or K-null phenotype 🩸
It is a rare phenotype that lacks all the Kell antigens on the surface of their RBCs. Individuals with the Ko or K-null phenotype produce an antibody called ‘anti-Ku’, which exhibits reactivity towards all other RBCs, except those with the Ko phenotype. This makes it incredibly challenging to get compatible blood for patients with the rare Ko phenotype.