Immunohematology最新文献

Anti-M is usually a naturally occurring antibody directed against M in the MNS blood group system. It does not require exposure to the antigen from previous transfusion or pregnancy. Anti-M is usually of the immunoglobulin M (IgM) isotype, binds best at about 4°C, binds well at room temperature, and rarely binds at 37°C. As a result of its lack of binding at 37°C, anti-M is usually clinically insignificant. There have been rare cases reported of an anti-M that reacts at 37°C. Such an exceptional anti-M may cause hemolytic transfusion reactions. We report a case of a warm-reactive anti-M and the investigational process used to identify it.

The high-prevalence blood group antigen, Sd^a, had been puzzling blood bankers and transfusionists for at least a decade when it was reported in 1967. The characteristic mix of agglutinates and free red blood cells (RBCs), caused by anti-Sd^a, is seen with the RBCs from 90 percent of individuals of European descent. However, only 2-4 percent of individuals are truly Sd(a-) and may produce anti-Sd^a. The antibodies, generally considered insignificant, may cause hemolytic transfusion reactions with high-expressing Sd(a+) RBCs (e.g., the unusual Cad phenotype, which can also be polyagglutinable). The Sd^a glycan, GalNAcβ1-4(NeuAcα2-3)Gal-R, is produced in the gastrointestinal and urinary systems, while its origin on RBCs is more controversial. According to current theory, Sd^a is likely to be passively adsorbed in low amounts, except in Cad individuals, where it has been found on erythroid proteins and at higher levels. The long-standing hypothesis that B4GALNT2 encodes the Sd^a synthase was confirmed in 2019, since homozygosity for a variant allele with rs7224888:C produces a non-functional enzyme associated with most cases of the Sd(a-) phenotype. Thereby, the SID blood group system was acknowledged as number 038 by the International Society of Blood Transfusion. Although the genetic background of Sd(a-) was settled, questions remain. The genetic background of the Cad phenotype has not yet been determined, and the source of the RBC-carried Sd^a is unknown. Furthermore, the interest of Sd^a stretches beyond transfusion medicine. Some tantalizing examples are lowered antigen levels in malignant tissue compared with normal tissue and interference with infectious agents like Escherichia coli, influenza virus, and malaria parasites.

Complexities of D within the Rh blood group system have long been recognized, initially using basic serologic testing and, more recently, using advanced and sensitive typing reagents. Discrepancies may arise when an individual carries a D antigen showing altered D antigen expression. These D variants are clinically important, since they may lead to production of anti-D in the carrier and induce alloimmunization in D- recipients, making their correct identification imperative. For clinical purposes, D variants can be classified into three groups: weak D, partial D, and DEL. The problem surrounding proper characterization of D variants exists because routine serologic tests are sometimes inadequate to detect D variants or resolve discrepant or ambiguous D typing results. Today, molecular analysis has revealed more than 300 RH alleles and is a better method for investigating D variants. Global distribution of variants differs, as observed in European, African, and East Asian populations. Discovery of the novel RHD*01W.150 (weak D type 150) with a nucleotide change of c.327_487-4164dup is proof. This variant, the result of an insertion of a duplicated exon 3 between exons 2 and 4 in the same orientation, was detected in more than 50 percent of Indian D variant samples in a 2018 study. The outcome of studies worldwide has led to the recommendation to manage D variant individuals as D+ or D- according to RHD genotype. The policies and workup with respect to D variant testing in donors, recipients, and prenatal women differ among blood banks, depending on type of variants predominantly encountered. Thus, a general genotyping protocol cannot be followed globally, and an Indian-specific RHD genotyping assay (multiplex polymerase chain reaction) designed to detect D variants frequently found in the Indian population was developed to save time and resources. This assay is also helpful for detecting several partial and null alleles. Identification of D variants by serology and characterization by molecular testing need to go hand-in-hand for better and safer transfusion practices.

To date, 43 blood group systems with 349 red blood cell (RBC) antigens have been recognized. The study of their distribution is useful for blood services to improve their supply strategies for providing blood of rare phenotypes, but also to design indigenous RBC panels for alloantibody screening and identification. In Burkina Faso, the distribution of extended blood group antigens is not known. This study aimed to investigate the extended profiles of blood group antigens and phenotypes of this population and to raise limitations and potential strategies for the design of local RBC panels. We conducted a cross-sectional study that included group O blood donors. Extended phenotyping for antigens in the Rh, Kell, Kidd, Duffy, Lewis, MNS, and P1PK systems was performed using the conventional serologic tube technique. The prevalence of each antigen and phenotype combination was determined. A total of 763 blood donors were included. The majority were positive for D, c, e, and k and negative for Fy^a and Fy^b. The prevalence of K, Fy^a, Fy^b, and C^w was less than 5 percent. The most frequent Rh phenotype was Dce, and the most common probable haplotype was R₀R₀ (69.5%). For the other blood group systems, the K-k+ (99.4%), M+N+S+s- (43.4%), and Fy(a-b-) (98.8%) phenotypes were the most frequent. Antigenic polymorphism of blood group systems by ethnicity and geography argues for the design and evaluation of population-sourced RBC panels to meet specific antibody profiles. However, some of the specificities identified in our study, such as the rarity of double-dose antigen profiles for certain antigens and the cost of antigen phenotyping tests, are major challenges to overcome.

Hemolytic disease of the fetus and newborn (HDFN) due to anti-D was severe and fatal before the development of RhD immune prophylaxis. Proper screening and universal administration of Rh immune globulin has decreased the incidence of HDFN to a great extent. Pregnancy, transfusion, and transplantation still increase the chances of other alloantibody formation and the potential for HDFN. Advanced methods for immunohematology investigation allow for the identification of alloantibodies causative for HDFN other than anti-D. Many antibodies have been reported to cause HDFN, but there is scant literature where isolated anti-C is responsible for HDFN. We present here a case of severe HDFN caused by anti-C leading to severe hydrops and death of the neonate despite three intrauterine transfusions and other measures.

Di^a is one of the most clinically significant low-prevalence antigens in the Diego blood group system, since antibodies to Di^a have, albeit rarely, been implicated in hemolytic transfusion reactions and hemolytic disease of the fetus and newborn (HDFN). Given the geographical association, most anti-Di^a HDFN cases have been reported in Japan, China, and Poland. We describe a case of HDFN in a neonate born to a 36-year-old G4P2012 woman of self-identified Hispanic ethnicity and of South American descent with multiple negative antibody detection tests in a U.S. hospital. Upon delivery, a cord blood direct antiglobulin test was positive (3+ reactivity), and neonatal bilirubin levels were moderately elevated, but phototherapy and transfusion were not required. This case highlights a rare, unexpected cause of HDFN in the United States secondary to anti-Di^a, given the near-universal absence of this antigen and antibody in most U.S. patient populations. The case also demonstrates the need for awareness of antibodies to antigens that are considered "low-prevalence" in most populations but that might be encountered more frequently in specific racial or ethnic groups and may require more extensive testing.