Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization.

The Augustine-negative alias At(a-) blood type, which seems to be restricted to people of African ancestry, was identified half a century ago but remains one of the last blood types with no known genetic basis. Here we report that a nonsynonymous single nucleotide polymorphism in SLC29A1 (rs45458701) is responsible for the At(a-) blood type. The resulting p.Glu391Lys variation in the last extracellular loop of the equilibrative nucleoside transporter 1 (ENT1; also called SLC29a1) is known not to alter its ability to transport nucleosides and nucleoside analog drugs. Furthermore, we identified 3 individuals of European ancestry who are homozygous for a null mutation in SLC29A1 (c.589+1G>C) and thus have the Augustine-null blood type. These individuals lacking ENT1 exhibit periarticular and ectopic mineralization, which confirms an important role for ENT1/SLC29A1 in human bone homeostasis as recently suggested by the skeletal phenotype of aging Slc29a1(-/-) mice. Our results establish Augustine as a new blood group system and place SLC29A1 as a new candidate gene for idiopathic disorders characterized with ectopic calcification/mineralization.

[Immunohematologic surveillance of the pregnant woman and the new prevention policy of anti-RH1 allo-immunization]. / La surveillance immunohématologique de la femme enceinte et la nouvelle politique de prévention de l'allo-immunisation anti-RH1.

Despite the generalization of immunoprophylaxis by anti-RH immunoglobulins since 1970 and improved management of at-risk pregnancies, allo-immunization due to the RH1 antigen (formerly known as Rhesus D or Rh D) remains widespread. In fact, anti-RH1 antibodies currently constitute over one-third of the immune antibodies detected after pregnancy. At the same time, allo-immunizations against others antigens than anti-RH1, especially anti-RH4 (anti-c) and anti-KEL1 (anti-Kell) increase. Allo-immunization, its follow-up during pregnancy, and its prevention are therefore still topical, and concern all the pregnant women. Immunohematological tests used in antenatal patients have gone a long way. However, despite a great deal of progress, we should not loose sight of the fact that these tests give only an indirect measurement and will only help the obstetrician, in conjunction with other fetal parameters to assess the severity of the haemolytic disease. The best method to assess the severity is the determination of the level of fetal hemoglobin after fetal blood sampling but this procedure is not without risk. Since 13 years, it is possible to determine the fetal RHD genotype of using amniocytes and to day directly with maternal plasma. All pregnant women should be blood-typed for ABO-RH-KEL1 and the blood tested for clinically irregular antibodies. The trend in anti-RH levels is more important than the level itself. Manual titration is simple but only provides rough, semiquantitative estimates of anti-RH concentration. Quantitative hemagglutination methods, using auto-analyzers and appropriate anti-RH1 standards, measured in mug/ml, are sensitive, rapid and have acceptable intra-laboratory reproducibility. RH:-1 women who are non-sensitized against RH1 antigen during and at the end of their pregnancy with a RH1 child. RH prophylaxis includes targeted prophylaxis after feto-maternal hemorrhage and now routine antenatal RH prophylaxis at the 28th week of gestation. It has been necessary to synthesize the indications of RH prophylaxis and immunohematological tests to assure an efficient therapeutic prevention.