Genetic background of anti‐CD99 producers in Japan and analysis of hemolytic transfusion reactions due to anti‐CD99

The XG blood group system comprises two antigens, Xga and CD99. CD99 is known to be carried on both the X and Y chromosomes in pseudoautosomal region 1. We identified five unrelated Japanese individuals with anti-CD99 and investigated their genomic background as well as the clinical significance of anti-CD99. Analysis of CD99 expression on RBCs and a modified monocyte monolayer assay was performed using flow cytometry. Genomic DNA was obtained from the five anti-CD99 producers to identify the deleted region responsible for the lack of CD99, and we conducted a long polymerase chain reaction using primer pairs specific for CD99 and GYG2. CD99 expression from the Y chromosome was higher than that from the X chromosome. The five anti-CD99 plasma samples gave varied agglutination strengths with the red blood cells (RBCs) expressing high and low CD99 levels, in the antiglobulin test. The phagocytosis rate of anti-CD99-sensitized RBCs was 76.6% in one case indicating a risk of hemolytic transfusion reactions (HTR), and it correlated with the level of CD99 expression. The deleted region spanned 115 kb, from CD99 exon 3 to GYG2 exon 1. All five anti-CD99 producers were homozygous for the large deletion allele. All five anti-CD99 producers were females with a history of pregnancy in Kyushu, Japan, and this deletion allele may thus be endemic. Our results indicated the possibility of HTR due to anti-CD99, and the risk is low when transfusing RBC products from Xg(a-) females with a low expression of CD99.