RESUMO
BACKGROUND: Antigens of the Knops blood group system are present on complement component (3b/4b) receptor 1 (CR1/CD35), which is a transmembrane glycoprotein encoded by the CR1 gene. Eight of the nine known antigens of this system are linked to polymorphisms in Exon 29. The molecular background of one antigen, York (Yk(a)), has not yet been described. STUDY DESIGN AND METHODS: We aimed to identify a polymorphism associated with the absence of Yk(a) to enable molecular typing. Yk(a)-negative individuals were identified by serologic typing. Their CR1 gene was partially sequenced and compared to that of Yk(a)-positive individuals. Loss of Yk(a) antigen was investigated by expressing the SCR22/23 domain of both wild-type and mutated CR1 as a GPI-linked protein on HEK293 cells. RESULTS: We observed that absence of the Yk(a) antigen is caused by a mutation in Exon 26 of the CR1 gene. This 4223C>T mutation results in a 1408T>M change at the protein level. Ten of 117 donors (8.5%) were homozygous TT, confirming the Caucasian frequency of 8% Yk(a)-negative individuals. Serologically, these TT donors showed a Yk(a)-negative phenotype, while CC/CT individuals were Yk(a)-positive. While the Yk(a) antigen was present on HEK293 cells expressing wild-type constructs, cells expressing the 4223C>T variant were Yk(a) negative. CONCLUSION: We identified a 4223C>T sequence variation in the CR1 gene causing absence of the Yk(a) antigen of the Knops blood group system. With this finding, all polymorphisms of the known Knops blood group antigens have been revealed, enabling molecular testing to contribute to red blood cell alloantibody identification procedures.