Kell and Kx blood group systems: an update

This review updates knowledge on the Kell (International Society of Blood Transfusion [ISBT] 006) and Kx (ISBT 019) blood group systems since the last review published in Immunohematology in 2015. It highlights new insights into the relationship between Kell glycoprotein and red blood cell (RBC) membrane stability, including recent discoveries of new antigens and alleles, and reporting of the first diagnosis of McLeod syndrome in an infant. The Kell and Kx blood group systems welcome an increasing number of antigens and/or alleles to their systems. Kell has a total of 38 antigens as of January 2025; a further 25 novel alleles encode K_mod phenotypes, and an additional 71 nucleotide changes are associated with the K₀ (null) phenotype. XK follows a similar theme with an ever-increasing number of new alleles, all encoding the Kx- (null) phenotype. The review emphasizes the role of molecular diagnostics in resolving serologic ambiguities in the blood bank or assisting the diagnosis of neurodegenerative syndromes. The monitoring and management of anti-K in pregnancy is evolving. Emerging technologies such as single-cell sequencing and multi-omics analysis workflows, gene editing, and cellular therapeutics may unlock the inner workings of Kell and Kx protein mechanics and elucidate the function of Kell protein biology, structural immunogenicity, and explain why alloanti-K is capable of suppressing erythroid growth.