RESUMEN
According to recent work group recommendations, individuals with the serologic weak D phenotypes should be RHD genotyped and individuals with molecular weak D types 1, 2, 3, 4.0, or 4.1 should be treated as D+. We report an African American woman with a long-standing history of metrorrhagia, who presented for infertility evaluation. Blood grouping showed AB with a possible subgroup of A, based on mixed-field agglutination, and a serologic weak D phenotype. Results from routine red cell genotyping for the RHD gene was incongruent with the serologic RhCE phenotype. For the surgical procedure, the patient was hence scheduled to receive group AB, D- RBC transfusions. Subsequent molecular analysis identified the ABO*A2.01 and ABO*B.01 alleles for the ABO genotype and the novel RHD allele [NG_007494.1(RHD):c.611T>A] along with an RHD*09.01.02 allele for the RHD genotype. Using a panel of monoclonal anti-D reagents, we showed the novel RHD(I204K) allele to represent a serologic weak D phenotype, despite occurring as a compound heterozygote, designated RHD*weak D type 161 (RHD*01W.161). Individuals with a weak D type 4.2 allele are prone to anti-D immunization, while the immunization potential of novel RHD alleles is difficult to predict. For now, patients should be treated as D- in transfusion and pregnancy management, when they harbor a novel RHD allele along with any weak D allele other than weak D types 1, 2, 3, 4.0, or 4.1. This study exemplifies strategies for how and when a laboratory should proceed from routine genotyping to nucleotide sequencing before any decisions on transfusion practice is made.
Asunto(s)
Tipificación y Pruebas Cruzadas Sanguíneas , Sistema del Grupo Sanguíneo Rh-Hr , Alelos , Transfusión Sanguínea , Femenino , Genotipo , Humanos , Fenotipo , Embarazo , Sistema del Grupo Sanguíneo Rh-Hr/genéticaRESUMEN
D- red blood cells (RBCs), always in short supply, and Rh immune globulin (RhIG) are not needed for patient care if D+ RBCs can safely be transfused. According to a recent work group recommendation, patients with the RHD*weak D type 4.0 allele can be considered D+. We report an African American woman who presented for delivery at the end of the third trimester, at which time anti-U and a serologic weak D phenotype were recognized, requiring U-, D- RBC units. We obtained 3 U- RBC units, including 1 D- unit. Later, the RHD*weak D type 4.0 allele was determined by RHD genotyping, only 6 days before delivery. The patient had an uneventful vaginal delivery of a D+ baby. No transfusion was needed for mother or baby. In this case, a pregnant woman with the RHD*weak D type 4.0 allele can safely be managed as D+, relaxing the unnecessary D- restriction for the limited U- RBC supply. The procured U-, D- RBC unit was frozen with 14 days of shelf-life remaining. To conserve D- RBC units, not limited to U-, for patients with a definite need, we recommend molecular analysis of a serologic weak D phenotype before a transfusion becomes imminent. The best time to resolve a serologic weak D phenotype with RHD genotyping is early in a pregnancy. Immunohematology 2021;37:1-4 .D red blood cells (RBCs), always in short supply, and Rh immune globulin (RhIG) are not needed for patient care if D+ RBCs can safely be transfused. According to a recent work group recommendation, patients with the RHD*weak D type 4.0 allele can be considered D+. We report an African American woman who presented for delivery at the end of the third trimester, at which time anti-U and a serologic weak D phenotype were recognized, requiring U, D RBC units. We obtained 3 U RBC units, including 1 D unit. Later, the RHD*weak D type 4.0 allele was determined by RHD genotyping, only 6 days before delivery. The patient had an uneventful vaginal delivery of a D+ baby. No transfusion was needed for mother or baby. In this case, a pregnant woman with the RHD*weak D type 4.0 allele can safely be managed as D+, relaxing the unnecessary D restriction for the limited U RBC supply. The procured U, D RBC unit was frozen with 14 days of shelf-life remaining. To conserve D RBC units, not limited to U, for patients with a definite need, we recommend molecular analysis of a serologic weak D phenotype before a transfusion becomes imminent. The best time to resolve a serologic weak D phenotype with RHD genotyping is early in a pregnancy. Immunohematology 2021;37:14 .
Asunto(s)
Sistema del Grupo Sanguíneo Rh-Hr , Globulina Inmune rho(D) , Alelos , Transfusión Sanguínea , Eritrocitos , Femenino , Genotipo , Humanos , Embarazo , Sistema del Grupo Sanguíneo Rh-Hr/genética , Globulina Inmune rho(D)/genéticaRESUMEN
The Working Party has met twice since the last report: in Seoul, South Korea 2014, and in London, UK 2015, both in association with the International Society of Blood Transfusion (ISBT) Congress. As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed. Eleven new blood group antigens were added to seven blood group systems. This brings the current total of blood group antigens recognized by the ISBT to 346, of which 308 are clustered within 36 blood groups systems. The remaining 38 antigens are currently unassigned to a known blood group system.
RESUMEN
We report on two patients with type 1 diabetes (T1D) after solitary islet transplantation in 2001. They received steroid-sparing immunosuppression (daclizumab, sirolimus, and tacrolimus according to the Edmonton protocol). Both patients became insulin independent for 2 years: Patient A, a 42-year-old female with a 12-year history of T1D, received two islet infusions; patient B, a 53-year-old female with a 40-year T1D history, received one islet infusion. Pretransplant, both had undetectable C-peptide concentrations and frequent and severe hypoglycemia. Pretransplant, hemoglobin A1c (HbA1c) was 7.8% and 8.8% and insulin requirements were 0.47 and 0.33 units/kg/day, respectively. Posttransplant, C-peptide levels remained detectable while immunosuppression was continued, but decreased over time. Insulin was re-started 2 years posttransplant in both patients. Since patient A's glycemia and insulin requirements trended toward pretransplant levels, immunosuppression was discontinued after 13 years. This resulted in a sudden cessation of C-peptide secretion. Patient B continues on immunosuppression, has better HbA1c, and half the insulin requirement compared to pretransplant. Both patients no longer experience severe hypoglycemia. Herein, we document blood glucose concentrations over time (>30 000 measurements per patient) and ß cell function based on C-peptide secretion. Despite renewed insulin dependence, both patients express satisfaction with having undergone the procedure.
Asunto(s)
Péptido C/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/cirugía , Terapia de Inmunosupresión/métodos , Trasplante de Islotes Pancreáticos/inmunología , Calidad de Vida , Adulto , Glucemia/análisis , Diabetes Mellitus Tipo 1/psicología , Femenino , Estudios de Seguimiento , Humanos , Trasplante de Islotes Pancreáticos/métodos , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Satisfacción del Paciente , Cuidados Posoperatorios/métodos , Medición de Riesgo , Muestreo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
The International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.
Asunto(s)
Antígenos de Grupos Sanguíneos/clasificación , Terminología como Asunto , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/inmunología , Humanos , Inmunogenética , Sociedades CientíficasRESUMEN
BACKGROUND/OBJECTIVES: Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by intravascular haemolysis with a negative direct antiglobulin test (DAT). Eculizumab is a humanized monoclonal antibody that inhibits complement component C5 and is approved for PNH treatment. Recent publications demonstrated that some patients with PNH develop a positive DAT during eculizumab treatment. These published clinical trials investigated a highly selected patient population. Therefore, it seems important to study this topic in a general PNH patient population with a longer follow-up. MATERIALS AND METHODS: We analysed haemolytic activity, RBC transfusion requirement, effect on DAT and ferritin levels in 41 patients with PNH before and during eculizumab therapy with a median follow-up of 24 months (range 1-63 months). RESULTS: During eculizumab therapy, median LDH decreased (1657-258 U/l; P < 0·0001), while median haemoglobin increased (9·2-10·3 g/dl). Eighteen of 32 pts (56%) who previously required regular transfusions became transfusion independent. DAT was positive for C3d in 72·4% of 21 eculizumab-treated pts with available DAT. Ferritin levels increased (69-348 ng/ml, P < 0·0001). This increase was more pronounced in pts with ongoing transfusion dependency during eculizumab therapy. CONCLUSION: Eculizumab therapy for PNH should be added to the list of possible causes for a positive DAT. Intravascular haemolysis was inhibited by eculizumab, but signs of extravascular haemolysis should be monitored. Because renal iron loss was stopped, eculizumab-treated pts can be prone to iron overload and therefore ferritin concentrations should be monitored closely.
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Anticuerpos Antiidiotipos/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Hemoglobinuria Paroxística/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Femenino , Ferritinas/sangre , Ferritinas/metabolismo , Hemoglobinuria Paroxística/sangre , Hemoglobinuria Paroxística/enzimología , Hemoglobinuria Paroxística/inmunología , Humanos , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/metabolismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
The Scianna system was named in 1974 when it was appreciated that two antibodies described in 1962 in fact identified antithetical antigens. However, it was not until 2003 that the protein on which antigens of this system are found and the first molecular variants were described. Scianna was the last previously serologically defined, protein-based blood group system to be characterized at the molecular level, marking the end of an era in immunohematology. This story highlights the critical role that availability of laboratory reagents for serologic testing has played in the initial characterization of a blood group and sets the stage for the development of new reagents, such as recombinant proteins, to assist in this process. The central role that genetics has played, both by classical pedigree analysis and by molecular techniques, in the discovery and characterization of this blood group is reviewed.
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Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/inmunología , Transfusión Sanguínea , Isoanticuerpos/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Tipificación y Pruebas Cruzadas Sanguíneas , Butirofilinas , Frecuencia de los Genes , Humanos , Isoanticuerpos/inmunología , Desequilibrio de Ligamiento , Datos de Secuencia Molecular , Mapeo Nucleótido , Linaje , Polimorfismo GenéticoAsunto(s)
Antígenos Bacterianos/inmunología , Antígenos de Superficie/inmunología , Enfermedad Granulomatosa Crónica/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Secuencia de Bases , Niño , Preescolar , Eliminación de Gen , Enfermedad Granulomatosa Crónica/genética , Enfermedad Granulomatosa Crónica/cirugía , Humanos , Lactante , MasculinoRESUMEN
PURPOSE OF THE STUDY: Ovarian hyperstimulation syndrome is a potentially life-threatening complication during controlled ovarian stimulation for fertility treatment. Since no association of this condition with ABO blood groups was known, we compared ABO antigens with severity and onset of symptoms in a case-control study. PATIENTS AND METHODS: One hundred and twenty-one patients, mainly Caucasians, were hospitalized because of ovarian hyperstimulation syndrome after receiving in vitro fertilisation, in the period from January 2000 to February 2007. Severity of symptoms, pregnancy rate and ABO blood group were collated. The ABO blood group distribution was compared to four independent control groups. RESULTS: Blood group A was markedly more frequent and blood group O less frequent in patients with ovarian hyperstimulation syndrome compared to the blood group distribution in all control cohorts. The odds ratio for patients undergoing controlled ovarian stimulation with blood group A versus O to develop the early-onset form of this condition was 2.171 (p-value 0.002). No association for late-onset form could be found. The overall pregnancy rate was 50.4% and three times higher in the group of late-onset ovarian hyperstimulation syndrome compared to the early-onset form. Four patients developed thromboses in the jugular or subclavian vein, none of whom had blood group O. CONCLUSION: Blood group A may be associated with early-onset ovarian hyperstimulation syndrome in Caucasians. Depending on further studies, this possible association may be considered for an individualized hormone dosing in controlled ovarian stimulation.
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Sistema del Grupo Sanguíneo ABO , Síndrome de Hiperestimulación Ovárica/sangre , Inducción de la Ovulación/efectos adversos , Femenino , Fertilización In Vitro/efectos adversos , Alemania/epidemiología , Humanos , Oportunidad Relativa , Síndrome de Hiperestimulación Ovárica/complicaciones , Síndrome de Hiperestimulación Ovárica/epidemiología , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Factores de Tiempo , Población BlancaRESUMEN
Immunological matching of a living related donor and recipient of an allograft is precise, but for cadaver organs matching is controversial, including at least detection of specific sensitization in the recipient against the donor, especially for HLA-DR. With the publication of some cases of ABO histoblood group incompatible transplantations with favorable outcomes, transplantation immunologists now focus on many of the 29 International Society of Blood Transfusion-approved histoblood group systems. So far, research lags behind knowledge about which system occurs in which organ, but modern molecular biology tests, like basic local alignment search tools (BLAST) and the recent inclusion of some systems into the CD classification, make possible the tracking of some histoblood group epitopes to specific tissue components. We have conducted such a search. With respect to tissue distribution, mRNA transcripts, and expressed sequence tags (EST), we observed a huge variety of distribution patterns. The total number of EST in the embryo pool was 752,991 and in the adult pool 1,227,835. Representative results were described for umbilical cord, bone marrow, peripheral stem cells, the nervous system, and the embryo. The ABO histoblood group systems maintain high priority for matching, because of the occurrence of naturally occurring anti-A/B antibodies. Substantial progress has been made in monitoring their levels and immunoglobulin isotypes in recipients, which, beyond hemagglutination, can now be quantitated using ELISA or cytofluorometry. A picture of ever-improving compatibility matching in solid organ and stem cell transplantation beyond mere HLA typing is the consequence.
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Antígenos HLA/genética , Prueba de Histocompatibilidad , Trasplante de Riñón/inmunología , Trasplante de Células Madre , Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Membrana Eritrocítica , Etiquetas de Secuencia Expresada , Antígenos HLA/inmunología , Humanos , Proteínas de la Membrana/sangre , Proteínas de la Membrana/genética , ARN Mensajero/genéticaRESUMEN
BACKGROUND: The RH genes RHD and RHCE encode two proteins that represent the clinically most important blood group system defined by the sequences of red cell membrane proteins. In the last five years the field has been moving from defining the underlying molecular genetics to applying the molecular genetics in clinical practice. MATERIALS AND METHODS: The state of the current knowledge is briefly summarized using recent reviews and original work since 2000. RESULTS: The RHD and RHCE genes are strongly homologous and located closely adjacent at the human chromosomal position 1p36.11. Part of the genetic complexity is explained by the clustered orientation of both genes with their tail ends facing each other. The SMP1 gene is located interspersed between both RH genes. Using additional genetic features of the RH gene locus, RHCE was shown to represent the ancestral RH position, while RHD is the duplicated gene. More than 150 alleles have been defined for RHD alone. They were classified based on antigenic and clinical properties into phenotypes like partial D, weak D and DEL. Among the D negative phenotype a large variety of non-functional alleles were found. The frequencies of these distinct alleles vary widely among human populations, which has consequences for clinical practice. CONCLUSION: Rhesus is a model system for the correlation of genotype and phenotype, facilitating the understanding of underlying genetic mechanisms in clustered genes. With regard to clinical practice, the genetic diagnostics of blood group antigens will advance the cost-effective development of transfusion medicine.
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Sistema del Grupo Sanguíneo Rh-Hr/genética , Alelos , Donantes de Sangre , Tipificación y Pruebas Cruzadas Sanguíneas , Eritroblastosis Fetal/genética , Eritroblastosis Fetal/prevención & control , Etnicidad/genética , Femenino , Asesoramiento Genético , Pruebas Genéticas , Genotipo , Humanos , Recién Nacido , Masculino , Modelos Moleculares , Fenotipo , Filogenia , Embarazo , Diagnóstico Prenatal , Isoinmunización Rh , Sistema del Grupo Sanguíneo Rh-Hr/química , Reacción a la TransfusiónAsunto(s)
Sistema del Grupo Sanguíneo Rh-Hr/química , Reacciones Antígeno-Anticuerpo , Proteínas Sanguíneas/química , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/inmunología , Intercambio Genético , Epítopos/química , Epítopos/genética , Epítopos/inmunología , Genes , Flujo Genético , Humanos , Isoanticuerpos/inmunología , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Modelos Moleculares , Mutación Missense , Fenotipo , Polimorfismo Genético , Conformación Proteica , Estructura Terciaria de Proteína , Grupos Raciales/genética , Sistema del Grupo Sanguíneo Rh-Hr/genética , Sistema del Grupo Sanguíneo Rh-Hr/inmunologíaRESUMEN
Fifty-seven IgG monoclonal anti-D antibodies were evaluated in the Rh flow cytometry section, in which 12 laboratories participated. Staining protocols and a fluorescein (FITC)-conjugated Fab fragment goat anti-human IgG (H + L) as a secondary antibody were recommended but not mandatory. A CcDEe red blood cell (RBC) sample that was shown to be homozygous for RHD by molecular methods was supplied and used as internal 'standard RBC' throughout all experiments. An RBC panel comprising two partial D and four weak D types was supplied as well. The use of standard RBC reduced the variability of the data among the laboratories and allowed the conversion of fluorescence data into epitope densities, which were compounded in an antigen density (antigen D per RBC). The highest antigen density was determined for DVI type III, followed by DVII and weak D type 3; the lowest antigen density were determined for weak D type 1 and type 2. Nine of the 12 participating laboratories discriminated three groups of aberrant RhD that had similar Rhesus indices (RI): D category VI with RI = 0; weak D type 2 and type 3 with an high RI; and D category VII and weak D type 1 with an intermediate RI. The antigen densities and the Rhesus indices obtained correlated well among the laboratories of this Workshop section despite different staining protocols, secondary antibodies and instrumentation.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Citometría de Flujo , Isoanticuerpos/inmunología , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Algoritmos , Animales , Presentación de Datos , Epítopos/genética , Epítopos/inmunología , Membrana Eritrocítica/inmunología , Citometría de Flujo/normas , Fluoresceína-5-Isotiocianato/análisis , Colorantes Fluorescentes/análisis , Fluorometría , Cabras , Humanos , Fragmentos Fab de Inmunoglobulinas/inmunología , Estándares de Referencia , Reproducibilidad de los Resultados , Sistema del Grupo Sanguíneo Rh-Hr/análisis , Sistema del Grupo Sanguíneo Rh-Hr/clasificación , Sistema del Grupo Sanguíneo Rh-Hr/genética , Globulina Inmune rho(D) , Manejo de Especímenes , Coloración y Etiquetado/métodosRESUMEN
BACKGROUND: The Colton blood group system (CO, ISBT 015) is composed of three antigens, of which Co3 (ISBT 015.003) is carried by almost all persons, except those of the extremely rare Co(a-b-) phenotype. The Colton blood group antigens are expressed by the water channel aquaporin 1 (aqp1; also known as channel-forming integral protein, CHIP-28), which is a highly conserved RBC integral membrane protein. The two most frequent alleles, CO1 and CO2, encode the antigens Co(a) and Co(b), respectively. Four null alleles have been described for the AQP1 gene to date. CASE REPORT: An Indian woman had an alloimmune antibody to an high-frequency antigen associated with mild HDN. Her RBCs were typed Co(a--b-), and the antibody was an anti-Co3. She typed CO1-positive and CO2-negative in a new genotyping method, using PCR with sequence-specific priming, for CO1 and CO2. A method for nucleotide sequencing of the four AQP1 exons from genomic DNA was developed. The patient was shown to be homozygous for a nonfunctional allele AQP1(232delG) that also carried the CO1-specific polymorphism. CONCLUSION: The kindred presented a fifth example of an AQP1 null allele, which was caused by a single nucleotide deletion leading to a shift in the reading frame beyond codon 78. A method of genotyping CO for Co(a) and Co(b) antigen phenotype prediction was presented.