Molecular analysis of patients with weak D and serologic analysis of those with anti-D (excluding type 1 and type 2).

Whether or not patients whose red blood cells (RBCs) carry certain weak D types produce anti-D, and if they do whether it is allo- or auto anti-D, remains controversial. The aim of this study was to determine the serologic features of anti-D in individuals expressing a weak D other than type 1 or type 2 and to assess whether the anti-D was an allo- or autoantibody. Serologic D typing and molecular analyses were performed on 748 individuals.

Systematic RH genotyping and variant identification in French donors of African origin.

Background: RH molecular analysis has enabled the documentation of numerous variants of RHD and RHCE alleles, especially in individuals of African origin. The aim of the present study was to determine the type and frequency of D and/or RhCE variants among blood donors of African origin in France, by performing a systematic RH molecular analysis, in order to evaluate the implications for blood transfusion of patients of African origin.

Materials And Methods: Samples from 316 African blood donors, whose origin was established by their Fy(a-b-) phenotype, were first analysed using the RHD and RHCE BeadChips Kit (BioArray Solutions, Immucor, Warren, NJ, USA).

Identification of novel silent KEL alleles causing KEL:-5 (Ko) phenotype or discordance between KEL:1,-2 phenotype/KEL*01/02 genotype.

Background: The Kell system, encoded by the KEL gene, is one of the most clinically important blood group systems. Molecular defects may lead to the absence of Kell antigen expression. The very rare KEL:5 results from silent KEL genes, also called KELnull alleles.

Molecular background of novel silent RHCE alleles.

Background: The absence of expression of C/c and E/e antigens has been associated with rare variant RHCE alleles, referred to as silent RHCE alleles, classically identified among individuals with a rare D- - or Rhnull phenotype. This work reports on different molecular mechanisms identified in three novel silent RHCE alleles.

Study Design And Methods: Samples from D- - or Rhnull individuals and their family members, from families for whom Rh phenotype and/or serologic data were unexplained by inheritance of conventional RH alleles, were analyzed.

RHD*DOL1 and RHD*DOL2 encode a partial D antigen and are in cis with the rare RHCE*ceBI allele in people of African descent.

Background: Several studies showed in people of African descent the existence of a genetic linkage between RHD alleles encoding a variant D antigen and a given altered RHCE*ce allele. RHCE*ceBI is a rare allele encountered in people of African descent, that encodes a Hr- hr(S) - Rhce protein. Our study shows that RHCE*ceBI appears to be genetically linked to two very similar variant RHD alleles, RHD*DOL1 and RHD*DOL2, and demonstrates for the first time that DOL-2 is a partial D antigen.

ABCB6 is dispensable for erythropoiesis and specifies the new blood group system Langereis.

The human ATP-binding cassette (ABC) transporter ABCB6 has been described as a mitochondrial porphyrin transporter essential for heme biosynthesis, but it is also suspected to contribute to anticancer drug resistance, as do other ABC transporters located at the plasma membrane. We identified ABCB6 as the genetic basis of the Lan blood group antigen expressed on red blood cells but also at the plasma membrane of hepatocellular carcinoma (HCC) cells, and we established that ABCB6 encodes a new blood group system (Langereis, Lan). Targeted sequencing of ABCB6 in 12 unrelated individuals of the Lan(-) blood type identified 10 different ABCB6 null mutations.

Null alleles of ABCG2 encoding the breast cancer resistance protein define the new blood group system Junior.

The breast cancer resistance protein, also known as ABCG2, is one of the most highly studied ATP-binding cassette (ABC) transporters because of its ability to confer multidrug resistance. The lack of information on the physiological role of ABCG2 in humans severely limits cancer chemotherapeutic approaches targeting this transporter. We report here that ABCG2 comprises the molecular basis of a new blood group system (Junior, Jr) and that individuals of the Jr(a-) blood type have inherited two null alleles of ABCG2.

Antibodies to co-trimoxazole (trimethoprim and/or sulfamethoxazole) related to the presence of the drug in a commercial low-ionic-strength solution.

Background: Drug-dependent antibodies have been associated with approximately 10% of acquired immune hemolytic anemia cases. These antibodies are a rare cause of interference in pretransfusion red blood cell (RBC) serologic testing. The aim of this work was to report three cases of subjects developing antibodies against co-trimoxazole, a combination of trimethoprim (TMP) and sulfamethoxazole (SMX).

Proof of principle for transfusion of in vitro-generated red blood cells.

In vitro RBC production from stem cells could represent an alternative to classic transfusion products. Until now the clinical feasibility of this concept has not been demonstrated. We addressed the question of the capacity of cultured RBCs (cRBCs) to survive in humans.

CPAP for acute cardiogenic pulmonary oedema from out-of-hospital to cardiac intensive care unit: a randomised multicentre study.

Purpose: Continuous positive airway pressure (CPAP) is a useful treatment for patients with acute cardiogenic pulmonary oedema (CPE). However, its usefulness in the out-of-hospital setting has been poorly investigated and only by small and single-centre studies. We designed a multicentre randomised study to assess the benefit of CPAP initiated out of hospital.

Anti-D investigations in individuals expressing weak D Type 1 or weak D Type 2: allo- or autoantibodies?

Background: Whether anti-D produced by individuals with a weak D phenotype are allo- or autoantibodies remains a matter of debate even though blood transfusion practice is impacted. The aim of our study was to determine the serologic features of anti-D in individuals expressing the most frequent weak D type in Caucasians that are weak D Type 1 or weak D Type 2, to assess whether anti-D were allo- or autoantibodies.

Study Design And Methods: Serologic D typing and molecular analysis enabled the including of 121 weak D Type 1 individuals and 99 weak D Type 2 individuals in our study.

Analysis of RhCE variants among 806 individuals in France: considerations for transfusion safety, with emphasis on patients with sickle cell disease.

Background: DNA testing has enabled the documenting of numerous variants of RHCE alleles, especially in individuals of African origin. The risk for production of clinically significant alloantibodies to Rh antigens of patients carrying variant RHCE alleles has led us to analyze the different RhCE variants investigated by molecular biology. Alloimmunization was analyzed regarding the RHCE genetic profile.

Noninvasive diagnosis of pulmonary embolism.

Background: We designed a simple and integrated diagnostic algorithm for acute pulmonary embolism (PE). Diagnosis was based on clinical probability assessment, plasma D-dimer testing, then sequential testing to include lower limb venous compression ultrasonography, ventilation perfusion lung scan, and chest multidetector CT (MDCT) imaging.

Methods: We included 321 consecutive patients presenting at Brest University Hospital in Brest, France, with clinically suspected PE and positive d-dimer or high clinical probability.

Blood group genotyping by high-throughput DNA analysis applied to 356 reagent red blood cell samples.

Background: DNA analysis for the prediction of blood group antigen expression has broad implications in transfusion medicine. It may be of particular interest especially to detect variants, when antigen expression is weak or altered. The use of high-throughput DNA analysis has never been applied to donors whose red blood cells (RBCs) are selected for reagent RBCs.

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, Co(a) , Co(b) , 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.

Cardiac multislice spiral computed tomography as an alternative to coronary angiography in the preoperative assessment of coronary artery disease before aortic valve surgery: a management outcome study.

Background: Conventional coronary angiography (CA) is still recommended before valvular surgery. Preliminary studies suggest that multislice spiral computed tomography coronary angiography (MSCT-CA) can be used to rule out coronary artery disease (CAD).

Aim: To assess prospectively the safety of ruling out CAD before surgery solely on the basis of normal MSCT-CA in patients with severe aortic valve disease.

Analysis of complement receptor type 1 expression on red blood cells in negative phenotypes of the Knops blood group system, according to CR1 gene allotype polymorphisms.

Background: The KN blood group system, which consists of nine antigen specificities, is located on complement receptor Type 1 (CR1/CD35). CR1, a complement regulatory protein, acts as a vehicle for immune complex clearance. CR1 exhibits a red blood cell (RBC) density polymorphism.

Door-to-balloon delays before primary angioplasty in the Regional Acute Myocardial Infarction Registry of Brittany. An analysis of the Observatoire Régional Breton sur l'Infarctus du myocarde (ORBI).

Background: Minimizing delays to coronary reperfusion is critical in the management of acute myocardial infarction (AMI).

Aims: To determine delays in in-hospital management and factors associated with delays of over 45min.

Methods: We analysed data from the Observatoire Régional Breton sur l'Infarctus, a registry of AMI patients admitted within 24h of symptom onset (July 2007 to December 2008) to an interventional cardiology centre in Brittany.

Anti-HrB and anti-hrb revisited.

Background: Since their description in the 1970s, anti-Hr(B) (antibody against a high-prevalence Rh antigen) and anti-hr(B) (anti-e-like antibody) are still a subject of debate about representing two aspects of a global immune response or being two independent antibodies.

Study Design And Methods: The aim of this study was to evaluate the immune response against the antigens of Rh system of 30 individuals presenting a hr(B)(RH31)- phenotype. Genomic analysis of RH genes was performed in all individuals.

Alloanti-c/ce in a c+ceAR/Ce patient suggests that the rare RHCE ceAR allele (ceAR) encodes a partial c antigen.

Background: ceAR (RHCE ceAR) is a rare RH allele encountered in people of African/Caribbean ancestry, known to encode a partial e antigen. The homozygous ceAR/ceAR genotype encodes the rare blood group Hr-. This study describes alloanti-c/ce in a ceAR/Ce patient, suggesting that ceAR also encodes a partial c antigen.

Alloanti-c (RH4) revealing that the (C)ce s haplotype encodes a partial c antigen.

Background: In the Rh blood group system, published observations showed that the c antigen has the fewest variant forms of the principal antigens in this system. The partial nature of the c antigen was only reported in c+ Rh:-26 persons and to be associated with the ce(s)(340) allele. This study reports the first case of alloanti-c related to a (C)ce(s) haplotype.

Identification and characterization of a novel XK splice site mutation in a patient with McLeod syndrome.

Background: McLeod syndrome is a rare X-linked neuroacanthocytosis syndrome with hematologic, muscular, and neurologic manifestations. McLeod syndrome is caused by mutations in the XK gene whose product is expressed at the red blood cell (RBC) surface but whose function is currently unknown. A variety of XK mutations has been reported but no clear phenotype-genotype correlation has been found, especially for the point mutations affecting splicing sites.

Heterogeneous molecular background of the weak C, VS+, hr B-, Hr B- phenotype in black persons.

Background: The rare Hr(B)- phenotype is encoded by the (C)ce(s) haplotype when present at the homozygous state. This haplotype contains two altered genes: a hybrid RHD-CE-D(s) gene segregated with a ce(s) allele of RHCE (733C>G and 1006G>T substitutions in Exon 5 and Exon 7 respectively). The aim of this study was to further investigate the molecular background of the (C)ce(s) haplotype.