An update on the Knops blood group system.

This update of the Knops (KN) blood group system (Moulds JM. The Knops blood group system. Immunohematology 2010;26:2-7) adds no new antigens to this system (International Society of Blood Transfusion system 22), which currently has nine antigens.

Two complement receptor one alleles have opposing associations with cerebral malaria and interact with αthalassaemia.

Malaria has been a major driving force in the evolution of the human genome. In sub-Saharan African populations, two neighbouring polymorphisms in the Complement Receptor One () gene, named and , occur at high frequencies, consistent with selection by malaria. Previous studies have been inconclusive.

Whole-exome sequencing of sickle cell disease patients with hyperhemolysis syndrome suggests a role for rare variation in disease predisposition.

Background: Hyperhemolysis syndrome (HHS) is an uncommon, but life-threatening, transfusion-related complication of red blood cell transfusion. HHS has predominantly been described in patients with sickle cell disease (SCD) and is difficult to diagnose and treat. The pathogenesis of HHS, including its occurrence in only a subset of apparently susceptible individuals, is poorly understood.

Inhibition of phagocytic recognition of anti-D opsonized Rh D+ RBC by polymer-mediated immunocamouflage.

The Rh D antigen posed both a significant clinical risk and inventory supply issue in transfusion medicine. The successful development of the immunocamouflaged RBC has the potential to address both the risk of acute anti-D transfusion reactions and to improve D- blood inventory in geographic locations where D- blood is rare (e.g.

Paroxysmal cold hemoglobinuria due to an IgA Donath-Landsteiner antibody.

Paroxysmal cold hemoglobinuria (PCH) is an autoimmune hemolytic anemia (AIHA) characterized by the presence of a Donath-Landsteiner (D-L) antibody. PCH occurs most commonly in young children and is associated with acute, often self-limited hemolytic anemia. The D-L antibody is classically a biphasic IgG anti-P autoantibody identified by the D-L test.

A multicenter study on the performance of a fully automated, walk-away high-throughput analyzer for pretransfusion testing in the US population.

Background: Moving to automation is a major focus of transfusion centers. Erytra (Grifols) is a walk-away analyzer with high-performance and -throughput capacity for pretransfusion testing. Efficiency and performance of Erytra with its cards and reagents were evaluated in comparison to Food and Drug Administration (FDA)-approved reference methods.

A Genome-Wide Screen for Large-Effect Alloimmunization Susceptibility Loci among Red Blood Cell Transfusion Recipients with Sickle Cell Disease.

Background: A selective susceptibility of certain individuals to form multiple alloantibodies in response to red cell transfusion is well-recognized in clinical practice, and is a particular problem in persons with sickle cell disease (SCD). The reason for this differential susceptibility is unclear, but inter-individual genetic differences are likely to contribute.

Methods: We conducted a pilot case-control genome-wide association study using 1,000,000 SNPs in 94 alloimmune responders (cases) and non-responders (controls) with SCD in order to identify loci of large effect size associated with alloimmunization.

A comparison of methods for the detection of the r'(s) haplotype.

Background: The r'(s) haplotype is found in 5% to 15% of individuals of African descent. Persons with this haplotype have a partial C antigen and weakened e and can produce anti-C or other "e-like" alloantibodies. Thus, for these chronically transfused patients, accurate detection of the r'(s) haplotype is important for selection of matched units.

A novel JK null allele associated with typing discrepancies among African Americans.

The Jknun (Jk-3) phenotype, attributable to null or silenced alleles, has predominantly been found in persons of Polynesian descent. With the increased use of molecular genotyping, many new silencing mutations have been identified in persons of other ethnic backgrounds. To date, only two JK null alleles have been reported in African Americans, JK*01N.

New RHCE variant alleles encoding the D- - phenotype.

Background: Variant alleles that do not produce RhCE antigens are rare. Consequently, they pose a challenge to transfusion when found in alloimmunized patients and make blood units valuable when found in donors.

Study Design And Methods: Five index cases and their relatives were studied by both serologic and molecular techniques.

Three novel alleles in the Kell blood group system resulting in the Knull phenotype and the first in a Native American.

Background: Antibodies to Kell antigens can be clinically important but only limited data are published regarding anti-Ku. Missense nucleotide changes in KEL account for the numerous Kell antigens, the K(mod) phenotype, and even the K(null) phenotype.

Study Design And Methods: DNA and RNA were extracted from white blood cells and polymerase chain reaction-based assays, cloning, and sequencing were done using standard protocols.

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.

Circulating Immune Complex Levels are Associated with Disease Severity and Seasonality in Children with Malaria from Mali.

Complement receptor one (CR1) is essential for removing circulating immune complexes (CIC), with malaria infection contributing to the formation of large amounts of CIC. We investigated CIC levels in children with malaria, of varying severity and seasonality. Two hundred age and sex-matched severe and mild malaria cases were studied during and after active disease.

A novel JKA allele, nt561C>A, associated with silencing of Kidd expression.

Background: The Jk(a-b-) null phenotype is not common but is more prevalent in Polynesian and Asian persons and appears to be rare in blacks. We determined the molecular basis for Jk(a-b-) in an African American family. DNA testing of samples from random African American, Caucasian, and Brazilian blacks was done to estimate the allele frequency.

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.

Future of molecular testing for red blood cell antigens.

When one looks at the field of molecular pathology or transplantation, it is evident that molecular biology has made a positive impact on medicine. However, the progress in transfusion medicine has been slower and more cautious than in other areas of the clinical laboratory. To understand where the field may go in the next 10 years requires that the reader understand what technology is available now.

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).

Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting.

Malaria has been a major selective force on the human population, and several erythrocyte polymorphisms have evolved that confer resistance to severe malaria. Plasmodium falciparum rosetting, a parasite virulence phenotype associated with severe malaria, is reduced in blood group O erythrocytes compared with groups A, B, and AB, but the contribution of the ABO blood group system to protection against severe malaria has received little attention. We hypothesized that blood group O may confer resistance to severe falciparum malaria through the mechanism of reduced rosetting.

Complement receptor 1 polymorphisms associated with resistance to severe malaria in Kenya.

Background: It has been hypothesized that the African alleles Sl2 and McCb of the Swain-Langley (Sl) and McCoy (McC) blood group antigens of the complement receptor 1 (CR1) may confer a survival advantage in the setting of Plasmodium falciparum malaria, but this has not been demonstrated.

Methods: To test this hypothesis, children in western Kenya with severe malaria-associated anaemia or cerebral malaria were matched to symptomatic uncomplicated malaria controls by age and gender. Swain-Langley and McCoy blood group alleles were determined by restriction fragment length polymorphism and conditional logistic regression was carried out.

Genetic mechanisms of Rhesus box variation.

Background: The RHD gene is flanked by two highly homologous DNA segments of approximately 9000 bp, the upstream and downstream Rhesus boxes. In haplotypes with an RHD deletion, the fusion of the two Rhesus boxes generates the single-hybrid Rhesus box, the detection of which has been applied for RHD zygosity determination. Aberrant Rhesus boxes can confound this application and appear to be frequent among African individuals.