Background/Case Studies: The McLeod phenotype is defined as the absence of the Kx antigen from the red blood cell (RBC) membrane. Kx is the only antigen in the XK blood group system. The Kx antigen is located on the Xk protein, which is linked to the KEL glycoprotein by a single disulfide bond. Absence of the Kx antigen leads to weakened expression of Kell system antigens and acanthocytosis. The McLeod phenotype is X-linked recessive and appears almost exclusively in males. Female carriers of the McLeod phenotype will express mixed RBC populations of normal Kell antigen expression and McLeod phenotype cells. Chronic granulomatous Disease (CGD) has been associated with the McLeod phenotype as they are both induced by genetic deletions on the X chromosome. Those with CGD McLeod type are able to produce anti-KL (anti-Kx + anti-Km). Those of the non-CGD McLeod type are able to produce anti-Km.
Here we will review a case where a McLeod phenotype donor was discovered during routine donor antigen screening in the IRL.
Study Design/Methods: During routine mass antigen screening of donor blood by the American Red Cross Reference Laboratory in Tucson, Arizona, a source of anti-Kpb was included with a batch of units. One donor sample preliminarily tested negative for the Kpb antigen. This donor was additionally tested with a source of anti-Kpa with the expectation the result would be positive, but instead a negative result was obtained. The donor sample was re-tested with anti-K, anti-k, anti-Kpa, anti-Kpb, and anti-Jsb antisera to investigate the irregularity. A negative result was obtained for all testing, except anti-k which produced very weak macroscopic agglutinates. The negative results were examined microscopically for confirmation, at which point microscopic agglutination was noted with anti-Kpb and anti-Jsb. It was also noted during microscopic evaluation that every cell in the field appeared crenated like burr cells. Suspecting sample contamination, a fresh 3% suspension of washed RBCs was prepared, and a drop placed on a slide for microscopic examination. Again, every cell in the fields examined appeared as burr cells.
Due to a lack of rare antisera in the current lab, the unit was shipped to the American Red Cross in Southern California for confirmation of a suspected McLeod phenotype. The remaining donor retention tube was shipped to the National Molecular Lab in Philadelphia for additional investigation.
Results/Findings: Additional testing performed by the Southern California laboratory included antigen typing with a source of anti-k, anti-Kpb, anti-Jsb, and anti-KL. Weakly reactive results were obtained with anti-k, anti-Kpb, and anti-Jsb. A negative result was obtained with anti-KL, serologically confirming the McLeod phenotype. Results of the molecular testing are summarized below.
Conclusions: This donor was confirmed serologically to lack the Kx antigen and have the McLeod phenotype. Multiple known genetic variations can lead to the McLeod phenotype, but this donor did not appear to have any of them. It is possible this donor has a genetic alteration in a region we are currently unable to test for, or it is possible he has a novel genetic mutation leading to the McLeod phenotype. According to medical literature, males with the McLeod phenotype typically have a compensated hemolytic anemia; but this donor had a normal hemoglobin/hematocrit and qualified as a blood donor. Additional follow-up with the donor was performed, along with explanation of his rare type and potential future health complications linked to this particular antigen type. This donor has been able to donate 38 times successfully since the discovery of his rare type in 2012 and further support the American Rare Donor Program. Four of his donations have been used to support a child with McLeod syndrome and CGD during bone marrow transplant.
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Russo, DC, et al. First example of anti-Kx in a person with the McLeod phenotype and without chronic granulomatous disease. Transfusion 40, 1371-1375, 2000.