Henry VIII, the Kell blood group system and the McLeod syndrome
Posted Mar 04 2011 1:00pm
ScienceDaily (Mar. 3, 2011) — Blood group incompatibility between Henry VIII and his wives could have driven the Tudor king's reproductive woes, and a genetic condition related to his suspected blood group could also explain Henry's dramatic mid-life transformation into a physically and mentally-impaired tyrant who executed two of his wives.
Fascinating medical history article! The Kell blood group system is probably the third most important blood group system (after ABO and Rh) because Kell antigens are highly immunogenic and Kell antibodies can cause hemolytic transfusion reactions and hemolytic disease of newborn. Fortunately, only about 9% of whites and 2% of blacks are K positive; so although K antibodies are relatively common, it is also relatively easy to obtain K-negative blood for transfusion.
The Kell antigens are carried by a red cell membrane glycoprotein with a large globular extracellular C-terminal component. The Kell protein interacts with the RBC surface membrane with a 37 kD protein XK (Kx antigen) which plays a key role in the expression of Kell antigens. Interestingly, the gene encoding XK is located on the petite arm of the X chromosome and is near the foci for X-linked chronic granulomatous disease (CGD) and Duchenne muscular dystrophy (DMD).
The McLeod phenotype is a rare but clinically interesting variant in the Kell blood group system. Individuals with this phenotype lack the Kx antigen and thus express reduced levels of Kell antigens. This phenotype is associated with acatholytic RBC morphology and low-grade chronic hemolytic anemia. Neuromuscular symptoms, as discussed in the article above with respect to good ol' 'enry, are frequently reported in patients with McLeod syndrome and may be related to lack of Kx expression. Finally, the McLeod phenotype is associated with other rare syndromes, most frequently (as one might expect) with CGD and DMD or Becker muscular dystrophy.