An update on the CD59 blood group system.

This update of the CD59 blood group system (Weinstock C, Anliker M, von Zabern I. CD59: a long-known complement inhibitor has advanced to a blood group system. Immunohematology 2015;31:145-51) increases the number of reported patients with CD59 deficiency from 10 to 14.

Complement activation by human red blood cell antibodies: hemolytic potential of antibodies and efficacy of complement inhibitors assessed by a sensitive flow cytometric assay.

Background: Therapeutic intervention strategies in complement-mediated hemolytic diseases are still inappropriate, and lethal events cannot be reliably prevented. As an in vitro model of intravascular hemolysis, a sensitive flow cytometric assay was designed using red blood cells (RBCs) of patients with paroxysmal nocturnal hemoglobinuria (PNH) as target cells. Complement activation by human allo- and autoantibodies directed against RBC antigens and the effect of different complement inhibitors were studied.

Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation.

Eculizumab inhibits the terminal, lytic pathway of complement by blocking the activation of the complement protein C5 and shows remarkable clinical benefits in certain complement-mediated diseases. However, several reports suggest that activation of C5 is not always completely suppressed in patients even under excess of eculizumab over C5, indicating that residual C5 activity may derogate the drug's therapeutic benefit under certain conditions. By using eculizumab and the tick-derived C5 inhibitor coversin, we determined conditions ex vivo in which C5 inhibition is incomplete.

CD59: A long-known complement inhibitor has advanced to a blood group system.

The blood group system number 35 is based on CD59, a 20-kDa membrane glycoprotein present on a large number of different cells, including erythrocytes. The major function of CD59 is to protect cells from complement attack. CD59 binds to complement components CS and C9 and prevents the polymerization of C9, which is required for the formation of the membrane attack complex (MAC).

A new blood group antigen is defined by anti-CD59, detected in a CD59-deficient patient.

Background: CD59 is a cell surface glycoprotein of approximately 20 kDa limiting the lytic activity of the terminal complement complex C5b-9. Although CD59 is known as a red blood cell (RBC) antigen defined by monoclonal antibodies, it so far has not been identified as a blood group antigen, since the description of a human alloantibody was missing. In this study we show the presence of an anti-CD59 in a patient affected by a homozygous CD59 deficiency.

Molecular basis of two novel and related high-prevalence antigens in the Kell blood group system, KUCI and KANT, and their serologic and spatial association with K11 and KETI.

Background: The numerous antigens in the Kell blood group system result from missense nucleotide changes in KEL. Antibodies to antigens in this system can be clinically important. We describe six probands whose plasma contained antibodies to high-prevalence Kell antigens and discuss their relationship.

D category IV: a group of clinically relevant and phylogenetically diverse partial D.

Background: The D typing strategies in several European countries protect carriers of D category VI (DVI) from anti-D immunization but not carriers of other partial D. Besides DVI, one of the clinically most important partial D is D category IV (DIV). A detailed description and direct comparison of the different DIV types was missing.

RhCE protein variants in Southwestern Germany detected by serologic routine testing.

Background: Variant RHCE alleles with diminished expression of C, c, E, and e antigens have been described and indicate the genetic diversity of this gene locus in several populations. In this study the molecular background of variant RhCE antigens identified by standard serologic routine testing in German blood donors and patients was determined.

Study Design And Methods: Samples from blood donors and patients were routinely analyzed for RhCE phenotype using the PK7200 analyzer with two sets of monoclonal anti-C, -c, -E, and -e reagents.

D variants at the RhD vestibule in the weak D type 4 and Eurasian D clusters.

Background: One branch of the RHD phylogenetic tree is represented by the weak D type 4 cluster of alleles with F223V as the primordial amino acid substitution. F223V as well as a large number of further substitutions causing D variants are located at the extracellular RhD protein vestibule, which represents the entrance to the transmembraneous channel of the RhD protein.

Study Design And Methods: RHD and RHCE nucleotide sequences were determined from genomic DNA and cDNA.

Six years' experience performing RHD genotyping to confirm D- red blood cell units in Germany for preventing anti-D immunizations.

Background: Red blood cell (RBC) units of D+ donors are falsely labeled D- if regular serologic typing fails to detect low D antigen expression or chimerism. The limitations of serology can be overcome by molecular typing.

Study Design And Methods: In January 2002, we introduced a polymerase chain reaction (PCR)-based assay for RHD as a routine test for first-time donors who typed D- by serologic methods including the indirect antiglobulin test.

The Bloodgen Project of the European Union, 2003-2009.

The Bloodgen project was funded by the European Commission between 2003 and 2006, and involved academic blood centres, universities, and Progenika Biopharma S.A., a commercial supplier of genotyping platforms that incorporate glass arrays.

DCS-1, DCS-2, and DFV share amino acid substitutions at the extracellular RhD protein vestibule.

Background: RhD and RhCE are structurally related to ammonium transporter proteins, yet their physiologic function remains unclear. Recent three-dimensional homology modeling with Escherichia coli AmtB as a template defined a putative transmembraneous channel. Three RhD variants with amino acid substitutions located at the extracellular channel aperture are described.