[en] The patient’s rare KEL:1,-2 phenotype was highlighted in course of a routine preoperative erythrocyte typing. Unexpectedly, her two daughters presented a KEL:-1,2 phenotype what appeared first as an apparent maternity exclusion. Flow cytometry, genotyping and adsorption-elution analyses were then performed for those 3 patients.
KEL genotyping showed that the patient’s genotype was KEL*01/KEL*02 whereas that of her daughters was KEL*02/KEL*02. By using polyclonal anti-KEL2 reagent, weak amount of KEL2 was identified on the patient’s erythrocytes, a result which was confirmed by both flow cytometry and adsorption-elution assays, suggesting that patient’s phenotype was in fact KEL:1,2w.
These results are in favour of a weak expressed KEL*02 allele (KEL*2mod) transmission coding for a KEL2 antigen detected in some technical conditions only. Those results allowed to explain the apparent maternity exclusion based on initial KEL phenotype. This study also seems to confirm the presence of a compensatory mechanism of the KELmod allele deficient expression in heterozygote patients.
A KEL phenotype retrospective study of 80.000 subjects showed a local KEL:1,-2 frequency four times lower than that described in literature. Moreover, a significant number of those individuals would in reality be KEL:1,2w, what still would decrease the real frequency of the KEL:1,2 subjects.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
MONFORT, Mélanie ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
PEYRARD, Thierry; Centre National de Référence pour les Groupes Sanguins > Paris, France
ARNAUD, Lionel; Institut National de la Transfusion Sanguine > Paris, France
HELIAS, Virginie; Institut National de la Transfusion Sanguine
MAGGIPINTO, Gianni ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
GERARD, Christiane ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Language :
French
Title :
Un allèle KEL*02mod responsable d'une exclusion apparente de maternité
Alternative titles :
[en] A KEL*02mod allele responsible for an apparent maternity exclusion
Coombs R., Mourant A., Race R. Detection of weak and "incomplete" Rh agglutinins; new test. Lancet 1945, 2:15-16.
Reid M.E., Lomas-Francis C. The blood group antigen facts book 2004, Elsevier Academic Press, New York. 2nd ed.
Yu L., Twu Y., Chang C., Lin M. Molecular basis of the Kell-null phenotype. J Biol Chem 2001, 276:10247-10252.
Wagner T., Resch B., Reiterer F., Gassner C., Lanzer G. Pancytopenia due to suppressed hematopoiesis in a case of fatal hemolytic disease of the newborn associated with anti-K supported by molecular K1typing. J Pediatr Hematol Oncol 2004, 26:13-15.
Klein H., Anstee D. Blood transfusion in clinical medicine 2006, Blackwell Science, Oxford. 11th ed.
Wagner T., Bernaschek G., Geissler K. Inhibition of megakaryopoiesis by Kell related antibodies. N Engl J Med 2000, 343:72.
Chiaroni J., Ferrera V., Dettori I., Roubinet F. Groupes sanguins érythrocytaires/Red-cell blood groups. EMC Hematol 2005, 2:53-112.
Ho M., Chelly J., Carter N., Danek A., Crocker P., Monaco A.P. Isolation of the gene for McLeod syndrome that encodes a novel membrane transport protein. Cell 1994, 77:869-880.
Lee S. Molecular basis of Kell blood group phenotypes. Vox Sang 1997, 73:1-11.
Russo D., Redman C., Lee S. Association of XK and Kell blood group proteins. J Biol Chem 1998, 273:13950-13956.
Allen F.H., Krabbe S.M.R., Corcoran P.A. A new phenotype (McLeod) in the Kell blood-group system. Vox Sang 1961, 6:555-560.
Jung H.H., Hergersberg M., Vogt M., Pahnke J., Treyer V., Röthlisberger B., et al. McLeod phenotype associated with a XK missense mutation without hematologic, neuromuscular, or cerebral involvement. Transfusion 2003, 43:928-938.
Bansal I., Jeon H.R., Hui S.R., Calhoun B.W., Manning D.W., Kelly T.J., et al. Transfusion support for a patient with McLeod phenotype without chronic granulomatous disease and with antibodies to Kx and Km. Vox Sang 2008, 94:216-220.
Jung H.H., Hergersberg M., Kneifel S., Alkadhi H., Schiess R., Weigell-Weber M., et al. McLeod syndrome: a novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings. Ann Neurol 2001, 49:384-392.
Wendel S., Fontão-Wendel R., Levi J.E., Aravechia M.G., Bordokan R.F., Russo D., et al. A McLeod phenotype detected by random screening for K:-4 [Kp(b-)] blood donors in Brazil. Transfusion 2004, 44:1579-1587.
Cartron J.P., Rouger P. Bases moléculaires des antigènes de groupes sanguins 1998, Masson, Paris.
Watkins C.E., Litchfield J., Song E., Jaishankar G.B., Misra N., Holla N., et al. Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome - a review. Clin Mol Allergy 2011, 9:13.
Wendel S., Fontão-Wendel R., Levi J.E., Aravechia M.G., Bordokan R.F., Russo D., et al. A McLeod phenotype detected by random screening for K:-4 (Kp(b-)) blood donors in Brazil. Transfusion 2004, 44:1579-1587.
Lee S., Russo D.C., Reiner A.P., Lee J.H., Sy M.Y., Telen M.J., et al. Molecular defects underlying the Kell null phenotype. J Biol Chem 2001, 276:27281-27289.
Körmöczi G.F., Wagner T., Jungbauer C., Vadon M., Ahrens N., Moll W., et al. Genetic diversity of KELnull and KELel: a nationwide Austrian survey. Transfusion 2007, 47:703-714.
Wester E.S., Steffensen R., Ligthart P.C., Vad J., de Haas M., Storry J.M., et al. KEL*02alleles with alterations in and around exon 8in individuals with apparent KEL:1-2phenotypes. Vox Sang 2010, 99:150-157.
Daniels G. Human blood group 2002, Blackwell Science, Oxford. 2nd ed.
Lee S., Russo D.C., Reid M.E., Redman C.M. Mutations that diminish expression of Kell surface protein and lead to the Kmod RBC phenotype. Transfusion 2003, 43:1121-1125.
Körmöczi G.F., Scharberg E.A., Gassner C. A novel KEL*1,3allele with weak Kell antigen expression confirming the cis-modifier effect of KEL3. Transfusion 2009, 49:733-739.
International Society for Blood Transfusion. Terminology for blood group alleles (December 2009). http://ibgrl.blood.co.uk/.
