John J. Moulds

The molecular diversity of Sema7A, the semaphorin that carries the JMH blood group antigens

BACKGROUND: Semaphorin 7A (Sema7A), the protein that carries the JMH blood group antigen, is involved in immune responses and plays an important role in axon growth and guidance. Because previous serologic studies on red blood cells (RBCs) suggested a considerable diversity of Sema7A, the present study was designed to elucidate the complex picture of the molecular diversity of this protein.

Knops blood group polymorphism and susceptibility to Mycobacterium tuberculosis infection

BACKGROUND: Complement receptor 1 (CR1) protein carries the Knops blood group antigens and is the receptor for the major ligand involved in Mycobacterium tuberculosis (Mtb) adhesion to macrophages. Erythrocyte CR1 binds immune complexes (ICs) formed during Mtb invasion, facilitating their clearance by the host immune system. The occurrence of specific Knops blood group genotypes among African populations was investigated to evaluate their impact on resistance or susceptibility to Mtb infection.

Two MER2‐negative individuals with the same novel CD151 mutation and evidence for clinical significance of anti‐MER2

BACKGROUND: MER2 (RAPH1), the only antigen of the RAPH blood group system, is located on the tetraspanin CD151. Only four examples of alloanti‐MER2 are known. We report here two new examples of alloanti‐MER2, in women of Pakistani and Turkish origin, one of whom showed signs of a hemolytic transfusion reaction (HTR) after transfusion of 3 units of red cells (RBCs).

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

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.

A functional AQP1 allele producing a Co(a–b–) phenotype revises and extends the Colton blood group system

BACKGROUND: The Colton blood group system currently comprises three antigens, Coa, Cob, and Co3. The latter is only absent in the extremely rare individuals of the Colton “null” phenotype, usually referred to as Co(a–b–), which lack the water channel AQP1 that carries the Colton antigens. The discovery of a Co(a–b–) individual with no AQP1 deficiency suggested another molecular basis for the Co(a–b–) phenotype.

Anti-EnaFS detected in the serum of an MiVII homozygote

Anti‐EnaFS was detected in the serum of a Caucasian woman, K.T., during her third pregnancy. She had not been transfused. At delivery, the infants red cells (RBCs) had a negative direct antiglobulin test. The antibody was inhibited by isolated MN sialoglycoprotein (SGP). Unlike other En(a—) cells, K.T.s EnaFS‐negative RBCs were found to demonstrate normal sialic acid levels, and an MN SGP exhibiting normal sodium dodecylsulphate electrophoretic mobility and periodic acid‐Schiff staining intensity. K.T., whose parents were consanguineous, appears to be the first known MiVII homozygote. In a three‐generation family study, MiVII was shown to travel with MS.

Swa: a subdivision.

Abstract. For some time, anomalous serological reactions have been observed when the same anti‐Swa sera are tested against red cells from different individuals reported as Sw(a+). A comparative collaborative study using the same collection of Sw(a+) cells and anti‐Swa sera was undertaken by 4 reference laboratories, and it was found that Swa represents a heterogeneous group of antigens that can be subdivided into two categories. Both categories, Sw(a+) 700:41 and Sw(a+) 700:‐41, were shown to be inherited.

Serological and Biochemical Investigations on the N.E. Variety of the Dantu Red Cell Phenotype

Studies during the last decade have established that the MNSs blood group locus corresponds to two, presumably adjacent, genes whiff encode the amino-acid sequences of two (MN and Ss) sialoglycoproteins (SGPs) or glycophorins (A and B) in human red cell (RBC) membranes (reviews: 1–4). The structural difference between the M and N antigens is determined by amino-acid polymorphisms at the 1st (Ser/Leu) and 5th (Gly/Glu) positions of the MN SGP, the complete sequence of which was elucidated (5–8). The sequence of the N-terminal 26 residues (res.) of the Ss SGP is identical with that of the N-specific MN SGP (8,9). This explains the occurrence of an additional N antigen, denoted as ‘N’, on the Ss SGP. A Met/Thr polymorphism at the 29th position of the Ss SGP represents the structural difference between the S and s antigens (8). Recently (10), the sequence of the intramembraneous domain (res. 36–72) of the Ss SGP was determined and found to be rather similar to the corresponding region (res. 65–101) of the MN SGP (Fig. 1).

Unexpected suppression of anti-Fya and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin.

BACKGROUND: Rh immune globulin (RhIG) has been used successfully for many years for the antenatal suppression of anti‐D in D– mothers carrying D+ babies to prevent hemolytic disease of the fetus and newborn. Although the mechanism of RhIG‐induced immunosuppression remains unknown, a recent report (TRANSFUSION 2006;46:1316‐22) has shown that women receiving RhIG produce elevated levels of transforming growth factor (TGF)β‐1, a powerful immunosuppressant cytokine. It was suggested that induction of TGFβ‐1 and immunosuppression may be independent of cognate antigen recognition by RhIG. Herein, we present a description of a mother and baby that supports this hypothesis.

Polyagglutinable NOR red blood cells found in an American family and a Polish family have the same unique glycosphingolipids

The inheritable NOR characteristic resulting in RBC polyagglutination was first found in an American family more than 20 years ago. The use of several lectins indicated that it is a new type of polyagglutination. The NOR RBCs were agglutinated by most ABO blood group–matched human sera; the agglutination was enhanced by treatment of RBCs with proteases and was inhibited by sheep hydatic cyst fluid and avian P1 glycoproteins. Several years ago a similar case of polyagglutination was found in a Polish family and was also called NOR. The features mentioned above suggested that the responsible antigen may be a glycolipid (exposed after proteolytic treatment of RBCs) terminating with Galα1,4 residue (present in P1 glycolipid). This was confirmed by finding in NOR RBCs two unique glycolipids reactive with Griffonia simplicifolia lectin IB4 (GSL-IB4, specific for αGal residues). The structure of these glycolipids was established; they were found to be globoside (GalNAcβ1-3Galα1-4Galβ1-4Glc-Cer) extension products. Three glycolipids were identified that represented globoside elongated with Galα1-4 (NOR1), GalNAcβ1-3Galα1-4 (NORint), and Galα14GalNAcβ1-3Galα1-4 (NOR2) units. Only the NOR1 and NOR2 glycolipids reacted with GSL-IB4 and human antiNOR. The NORint glycolipid was detected with GalNAcspecific soybean lectin (SBA). Human anti-NOR recognizing the Galα1-4GalNAcβ13Gal glycotope (terminal sequence of NOR1 and NOR2 glycolipids) were purified and characterized by means of synthetic oligosaccharides and glycoconjugates. Interestingly, two major types of antiNOR were identified, specific either to Galα1-4GalNAc/Galβ1-3Gal or to Galα1-4GalNAc. All antibodies crossreacted weakly with Galα1-4Gal, which explained the weak inhibition of agglutination by P1 glycoproteins. Two murine monoclonal anti-NOR, highly specific to Galα1-4GalNAc, were also obtained. Identification of the Polish case of polyagglutination as NOR was based on the weak inhibition of the polyagglutination by P1 glycoproteins. Therefore, it seemed interesting to compare glycosphingolipids of RBCs from both families. The neutral glycolipids from RBCs of the Polish (TS, blood group A) and American (TK, blood group B) NOR blood donors were purified and fractionated by high-performance thinlayer chromatography. The NOR-related glycolipids were then identified by overlaying the thin-layer plates with the monoclonal anti-NOR (nor118) and biotinylated lectins, GSL-IB4 and SBA, with the described procedures. The results shown in Fig. 1 indicated that both samples of NOR RBCs contain identical unique glycolipids. The monoclonal anti-NOR and GSL-IB4 stained strongly NOR1 and NOR2 glycolipids that migrated identically in both NOR samples and were absent in control blood group A and B RBCs. Weak additional bands stained with GSL-IB4 in NOR-TK RBC glycolipids represent blood group B glycolipids that are also present in control B RBCs and are known to react with GSL-IB4. Moreover, SBA, which reacted weakly with globoside in all studied samples, detected a glycolipid migrating between NOR1 and NOR2 in NOR-TS and NOR-TK samples, but not in control A and B RBCs. This glycolipid (NORint) was shown earlier to be a GalNAc-terminated precursor to NOR2. The NOR1 and NORint bands are also distinctly seen on the orcinolstained plate, indicating that these glycolipids are present in NOR RBCs in higher amounts than the NOR2 glycolipid. The genetic background of the NOR phenotype is not known yet, but it may be similar because the American donor has maternal German ancestry. Independently of whether the genetic alterations occurring in both families are identical or different, they lead to the same effect, that is, formation of identical unique globoside derivatives that are recognized by commonly present natural human antibodies.