Hemolytic disease of the fetus and newborn is most commonly caused by anti-D alloantibody. It is usually seen in Rhesus D (RhD)-negative mothers that have been previously sensitized. We report here a case of hemolytic disease of the fetus and newborn in a newborn baby caused by anti-D and anti-S alloantibodies, born to a mother who was RhD negative, but with no previous serological evidence of RhD alloimmunization.
A one-day-old Chinese baby boy was born to a mother who was group A RhD negative. The baby was jaundiced with hyperbilirubinemia, but with no evidence of infection. His blood group was group A RhD positive, his direct Coombs' test result was positive and red cell elution studies demonstrated the presence of anti-D and anti-S alloantibodies. Investigations performed on the maternal blood during the 22 weeks of gestation showed the presence of anti-S antibodies only. Repeat investigations performed post-natally showed the presence of similar antibodies as in the newborn and an anti-D titer of 1:32 (0.25 IU/mL), which was significant. A diagnosis of hemolytic disease of the fetus and newborn secondary to anti-D and anti-S was made. The baby was treated with phototherapy and close monitoring. He was discharged well after five days of phototherapy.
This case illustrates the possibility of an anamnestic response of allo-anti-D from previous sensitization in a RhD-negative mother, or the development of anti-D in mid-trimester. Thus, it highlights the importance of thorough antenatal ABO, RhD blood grouping and antibody screening, and if necessary, antibody identification and regular monitoring of antibody screening and antibody levels for prevention or early detection of hemolytic disease of the fetus and newborn, especially in cases of mothers with clinically significant red cell alloantibody.
The spectrum of hemolytic disease of the newborn has changed over the last few decades. With the implementation of Rhesus D immunoprophylaxis, hemolytic disease due to ABO incompatibility and other alloantibodies has now emerged as major causes of this condition. Though in developing countries, anti D is still a common antibody in pregnant women, many Asian countries have identified alloantibodies other than anti D as a cause of moderate-severe hemolytic disease. The most concerned fact is that, some of these have been described in Rh D positive women. It appears that universal antenatal screening in all pregnant women needs to be initiated, since Rh D positive women are just as likely as D negative women to form alloantibodies. Many developed nations have national screening programs for pregnant women. This is necessary to ensure timely availability of antigen negative blood and reduce effects on the newborn. Although universal screening seems justified, the cost and infrastructure required would be immense. Developing countries and under resourced nations need to consider universal antenatal screening and frame guidelines accordingly.
Newborn hemolytic disease; red cell alloimmunisation; antenatal antibody screening
Alloantibodies of clinical importance can cause transfusion reactions or hemolytic disease of the fetus and newborn (HDFN). The frequencies of these antibodies have not been reported in our locality.
To determine the frequency of occurrence of alloantibodies among pregnant women in Port Harcourt, Nigeria.
Settings and Design:
This is a prospective study, which was carried out in the Braithwaite Memorial Specialist Hospital, Port Harcourt, Nigeria.
Materials and Methods:
Screening and identification of red blood cell alloantibodies was done on the sera of 500 pregnant women using the DiaMed, DiaCell, and DiaPanel reagents (Cressier, Switzerland). ABO and Rh blood groups were done using antisera bought from Biotec (Ipswich, UK).
Alloantibodies were identified in the serum of 17 of the 500 (3.4%) pregnant women. The specificity of the antibodies was as follows: anti-C 6 (1.2%), anti-E 3 (0.6%), anti-Jsb 3 (0.6%), and anti-K 5 (1.0%). No anti-D was identified despite 8.6% of the study population being Rhesus D (Rh D) negative. The distribution of the antibodies was found to be independent of the blood groups of the participants (χ2 = 4.050, P = 0.670). Blood group O constituted the highest percentage (48.0%).
This study has identified the presence of non-Rh D antibodies to the proportion of 3.4%. Rh D antibody was absent in this population irrespective of the relatively high percentage of Rh D negative women. There is a need to determine the actual risk these antibodies may pose to the antenatal women and to include antibody screening and identification in routine antenatal care.
Alloantibodies; frequencies; non-Rh D antibodies; HDFN; Nigeria
In this study, we report the first Korean case of an anti-Gerbich (Ge) alloantibody to a high-incidence antigen that belongs to the Ge blood group system. The alloantibody was detected in a middle-aged Korean woman who did not have a history of transfusion. Her blood type was B+, and findings from the antibody screening test revealed 1+ reactivity in all panels except the autocontrol. The cross-matching test showed incompatible results with all 5 packed red blood cells. Additional blood type antigen and antibody tests confirmed the anti-Ge alloantibody. While rare, cases of hemolytic transfusion reaction or hemolytic disease in newborns due to anti-Ge have been recently reported in the literature. Therefore, additional further studies on alloantibodies to high-incidence antigens, including anti-Ge, are necessary in the future.
Ge; Blood group antigens; Transfusion
Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother's red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs.
We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting with severe anemia, thrombocytopenia, and conjugated hyperbilirubinemia, while the other had moderate anemia and unconjugated hyperbilrubinemia. Although both the neonates were treated by phototherapy and intravenous immunoglobulin, one of them received double volume exchange transfusion.
There appeared to be an increase in the occurrence of hemolytic disease of the fetus and newborn caused by Rh antibodies other than anti-D. In this case report, both patients presented with anemia and hyperbilirubinemia but were successfully treated, with a favorable outcome.
Allo-antibody; anti-E; hemolytic disease of the fetus and newborn
Universal screening of all antenatal women, including D antigen-positive pregnant ones, is mandatory in most developed countries. However, no guidelines on this issue are available for developing countries such as India. Furthermore, there is limited information on immunisation rates in pregnant women (D antigen-positive and D antigen-negative) from India. We, therefore, studied the prevalence of alloantibodies among multigravida women in India.
Materials and methods
In this prospective study, carried out to detect the prevalence of alloantibodies among multigravida women in India, 3,577 multigravida women attending antenatal clinics were typed for ABO and D antigens and screened for alloantibodies by column agglutination technology. The medical history and detailed obstetric history of these women were reviewed and information recorded on any prior haemolytic disease of the foetus and newborn among siblings and/or blood transfusions.
The overall prevalence of alloantibodies in this study was 1.25%. There was a statistically significant difference between alloimmunisation rates in the D antigen-negative and D antigen-positive groups (10.7% versus 0.12%, respectively). Anti-D antibody contributed to 78.4% of total alloimmunisations in our study.
Anti-D was the most common culprit responsible for alloimmunisation. Other alloantibodies found included anti-C, anti-M, anti-S and anti-c. Large-scale population-based studies are required to assess the real magnitude of alloimmunisation in pregnant women in India.
alloimmunisation; irregular erythrocyte antibodies; pregnancy
Transplacental or fetomaternal hemorrhage (FMH) may occur during pregnancy or at delivery and lead to immunization to the D antigen if the mother is Rh-negative and the baby is Rh-positive. This can result in hemolytic disease of the fetus and newborn (HDFN) in subsequent D-positive pregnancies. The aim of this study is to highlight the challenges associated with the effective management and prevention of Rh alloimmunization among Rh-negative women in Sub-Saharan Africa. In most Sub-Saharan African countries, there is poor and sometimes no alloimmunization prevention following potentially sensitizing events and during medical termination of pregnancy in Rh-negative women. Information about previous pregnancies and termination are often lacking in patients’ medical notes due to poor data management. These issues have made the management of Rh-negative pregnancy a huge challenge. Despite the fact that the prevalence of Rh-negative phenotype is significantly lower among Africans than Caucasians, Rh alloimmunization remains a major factor responsible for perinatal morbidity in Sub-Saharan Africa and may result in the compromise of the woman’s obstetric care due to the unaffordability of anti-D immunoglobulin. There is the urgent need for the implementation of universal access to anti-D immunoglobulin for the Rh-negative pregnant population in Africa. Anti-D immunoglobulin should be available in cases of potentially sensitizing events such as amniocentesis, cordocentesis, antepartum hemorrhage, vaginal bleeding during pregnancy, external cephalic version, abdominal trauma, intrauterine death and stillbirth, in utero therapeutic interventions, miscarriage, and therapeutic termination of pregnancy. There is also the need for the availability of FMH measurements following potentially sensitizing events. The low-cost acid elution method, a modification of the Kleihauer–Betke (KB) test, can become a readily available, affordable, and minimum alternative to flow cytometric measurement of FMH. Knowledge of anti-D prophylaxis among obstetricians, biomedical scientist, midwives, traditional birth attendants, pharmacists, and nurses in Africa needs to be improved. This will facilitate quality antenatal and postnatal care offered to Rh-negative pregnant population and improve perinatal outcomes.
rhesus isoimmunization; Sub-Saharan Africa; universal access; anti-D; management; Rh-negative women
Neonatal alloimmune neutropenia (NAN) is an uncommon disease of the newborn provoked by the maternal production of neutrophil-specific alloantibodies, whereby neutrophil IgG antibodies cross the placenta and induce the destruction of fetal neutrophils. Affected newborns are usually identified by the occurrence of bacterial infections. The most frequent antigens involved in NAN are the human neutrophil antigen-1a (HNA-1a), HNA-1b, and HNA-2a. We report a neonate who was delivered at 36 weeks and had a severe neutropenia but who responded well to recombinant human granulocyte colony-stimulating factor (rhG-CSF). Anti-HNA-1a antibody was identified by mixed passive hemagglutination assay in both the sera of the baby and the mother. The baby had HNA-1a and HNA-1b but the mother had only HNA-1b on granulocytes. This is the first Korean report of NAN in which the specificity of the causative antibody was identified.
Infant, Newborn; Neutropenia; neutrophil-specific antigen NA1, human; Antibodies
We report a case of two consecutive episodes of acute hemolytic transfusion reactions (HTRs) due to multiple alloantibodies in a 34-yr-old man who suffered from avascular necrosis of left femoral head. He received five units of packed red blood cells (RBCs) during surgery. Then the transfusion of packed RBCs was required nine days after the surgery because of the unexplained drop in hemoglobin level. The transfusion of the first two units resulted in fever and brown-colored urine, but he received the transfusion of another packed RBCs the next day. He experienced even more severe symptoms during the transfusion of the first unit. We performed antibody screening test, and it showed positive results. Multiple alloantibodies including anti-E, anti-c and anti-Jkb were detected by antibody identification study. Acute HTRs due to multiple alloantibodies were diagnosed, and the supportive cares were done for 6 days. We suggest the antibody screening test should be included in the panel of pretransfusion tests for safer transfusion, and it is particularly mandatory for the patients with multiple transfusions, pregnant women, and preoperative patients.
We are reporting a rare case of severe hemolytic disease of newborn (HDN) with Bombay phenotype mother. A retrospective study of a case with severe haemolytic disease of newborn with Bombay phenotype mother was done. Blood grouping, antibody screening, and lectin study was done on the blood sample of the baby and mother to confirm the diagnosis. Hematological and biochemical parameters were obtained from the hospital laboratory information system for the analysis. Blood group of the baby was A positive, direct antiglobulin test was negative. Blood group of the mother was confirmed to be Bombay phenotype, Hematological parameters showed all the signs of ongoing hemolysis and the bilirubin level was in the zone of exchange transfusion. Due to the unavailability of this rare phenotype blood unit, baby was managed conservatively. Anticipating the fetal anemia and HDN with mothers having Bombay phenotype and prior notification to the transfusion services will be of great help in optimizing the neonatal care and outcome.
Blood grouping; Bombay phenotype; hemolytic disease of newborn
Rhesus haemolytic disease of the newborn is a prototype of maternal isoimmunisation and fetal haemolytic disease. There are other rare blood group antigens capable of causing alloimmunisation and haemolytic disease such as c, C, E, Kell and Duffy. In India, after the confirmation of a newborn's blood group, antibodies are screened only if the mother is Rehsus D-negative negative and the father is Rhesus D-positive. Hydrops in Rhesus positive women are investigated along the lines of non-immune hydrops.
We report the case of a patient from India where irregular antibodies were requested for an O-positive 26-year-old mother in order to investigate fetal hydrops. Anti-c antibody was revealed and the fetus was treated successfully with compatible O negative and c negative intrauterine blood transfusions. The baby was treated postnatally with double volume exchange transfusion with the same compatible blood, and was discharged 30 days after birth.
We highlight the importance of conducting irregular antibody screening for women with significant obstetric history and fetal hydrops. This could assist in diagnosing and successfully treating the fetus with appropriate antigen negative cross-matched compatible blood. We note, however, that anti-c immunoglobulin is not yet readily available.
The Kell blood group system expresses high and low frequency antigens with the
most important in relation to transfusion including the antithetic KEL1 and KEL2;
KEL3 and KEL4; KEL6 and KEL7 antigens. Kell is a clinically relevant system, as it
is highly immunogenic and anti-KEL antibodies are associated with hemolytic
transfusion reactions and hemolytic disease of the fetus and newborn. Although
required in some situations, Kell antigen phenotyping is restricted due to
technical limitations. In these cases, molecular approaches maybe a solution. This
study proposes three polymerase chain reaction genotyping protocols to analyze the
single nucleotide polymorphisms responsible for six Kell antithetic antigens
expressed in a Brazilian population.
DNA was extracted from 800 blood donor samples and three polymerase chain
reaction-restriction fragment length polymorphism protocols were used to genotype
the KEL*1/KEL*2, KEL*3/KEL*4 and KEL*6/KEL*7 alleles. KEL*3/KEL*4 and KEL*6/KEL*7
genotyping was standardized using the NlaIII and MnlI restriction enzymes and
validated using sequencing. KEL*1/KEL*2 genotyping was performed using a
previously reported assay.
KEL genotyping was successfully implemented in the service; the following
distribution of KEL alleles was obtained for a population from southeastern
Brazil: KEL*1 (2.2%), KEL*2 (97.8%), KEL*3 (0.69%), KEL*4 (99.31%), KEL*6 (2.69%)
and KEL*7 (97.31%). Additionally, two individuals with rare genotypes, KEL*1/KEL*1
and KEL*3/KEL*3, were identified.
KEL allele genotyping using these methods proved to be reliable and applicable to
predict Kell antigen expressions in a Brazilian cohort. This easy and efficient
strategy can be employed to provide safer transfusions and to help in rare donor
Kell blood-group system; Molecular biology; Gene frequency; Erythrocytes; Polymerase chain reaction
We report a case of hemolytic disease in a newborn due to anti S antibodies. Baby R was born at term to an O+ mother whose antibody screen was positive for phenotype big S. Cord blood eluate revealed anti-S RBC; antigen: RBC typing for S- was positive. Physical examination of baby was unremarkable. The infant's HCT was 44.2 at 6 hours of age. At 48 hours, the HCT decreased to 33.5, bilirubin peaked to 5.4, retic had peaked to 6.8. By seven days, all these values reverted to the normal, and baby has remained asymptomatic.
Several irregular red blood cell alloantibodies, produced by alloimmunization of antigens in transfusions or pregnancies, have clinical importance because they cause hemolysis in the fetus and newborn and in transfused patients.
a prospective analysis of patients treated by the surgical and clinical emergency services of Hospital de Clínicas of the Universidade Federal do Triângulo Mineiro (HC/UFTM), Brazil was performed to correlate alloimmunization to clinical and epidemiological data.
Blood samples of 143 patients with initial negative antibody screening were collected at intervals for up to 15 months after the transfusion of packed red blood cells. Samples were submitted to irregular antibody testing and, when positive, to the identification and serial titration of alloantibodies. The Fisher Exact test and Odds Ratio were employed to compare proportions.
Fifteen (10.49%) patients produced antibodies within six months of transfusion. However, for 60% of these individuals, the titers decreased and disappeared by 15 months after transfusion. Anti-K antibodies and alloantibodies against antigens of the Rh system were the most common; the highest titer was 1:32 (anti-K). There was an evident correlation with the number of transfusions.
Given the high incidence of clinically important red blood cell alloantibodies in patients transfused in surgical and clinical emergency services, we suggest that phenotyping and pre-transfusion compatibilization for C, c, E, e (Rh system) and K (Kell system) antigens should be extended to all patients with programmed surgeries or acute clinical events that do not need emergency transfusions.
Blood transfusion; Blood group antigens; Hemolysis; Immunophenotyping; Emergencies
The red cells of 63 members of 11 families were tested with 125I-labeled anti-Rh0(D). Families with a history of hemolytic disease of the newborn due to fetomaternal Rh incompatibility were selected for study. In such families it was possible to determine the antibody binding to the Rh0(D) heterozygous red cells of the children and to compare within each family this value with the antibody bound to the father's Rh0(D)-positive red cells and the mother's Rh0(D)-negative red cells. The fathers in all the families studied could be assigned to two classes on the basis of the quantity of antibody bound to their red cells. One group bound about the same quantity of antibody to their cells as did their children, indicating that they were heterozygous for the Rh0(D) antigen. The other bound about twice as much antibody to their cells as did their children, indicating that they were homozygous for the antigen. The Rh genotype of the father in all 11 families could be ascertained by using the children in each family as a reference point. The members of two families showed a poor correspondence between antibody binding and zygosity. In one family an Rh heterozygous child (R1r) took up 85% of the antibody bound to the father's homozygous cells (R1R1), and in the other family an Rh heterozygous child (R1r) took up 20% more antibody than did the cells of her father, which were of the same Rh phenotype (Rh1) and zygosity.
The quantity of antibody bound to the red cells of unrelated Rh0(D) homozygous individuals of the same Rh phenotype (Rh1) showed an almost sixfold variation. A consequence of this observation was that the cells of Rh0(D) heterozygous children of high antibody uptake fathers took up more antibody than did the cells of low antibody uptake Rh0(D) homozygous fathers. The gene dosage effect for the Rh0(D) antigen demonstrable within a family does not appear to apply when unrelated individuals are tested, even though they may be of the same Rh phenotype.
Immunoprophylaxis with IgG anti-D is a standard prevention of hemolytic disease of the fetus and newborn. Fetal Rhesus D (RhD) blood group genotyping from maternal plasma of RhD-negative pregnant women allows targeted prophylaxis with IgG anti-D in RhD-positive pregnancies only. We set up a reliable protocol for prenatal RHD genotyping.
153 pregnant Caucasian RhD-negative women were tested in the 27th week (range 7–38th week) of pregnancy. 18 of them were alloimmunized to the RhD antigen. The fetal RHD genotype was determined based on an automated DNA extraction and real-time polymerase chain reaction method. Intron 4 and exons 5, 7 and 10 of the RHD gene and the SRY gene were targeted.
The fetal RhD status and gender was 100% correctly predicted in all 153 pregnancies (55 RhD-positive males, 45 RhD-positive females; 23 RhD-negative males, 30 RhD-negative females).
The accuracy and applicability of our protocol for non-invasive fetal RhD determination allows the correct management of RhD-incompatible pregnancies. Our protocol could prevent unnecessary immunoprophylaxis in 53 of 153 cases. We therefore recommend that non-invasive fetal RHD genotyping is introduced as an obligatory part of prenatal screening.
Noninvasive RHD typing; Fetal DNA; Maternal plasma
QUESTION: One of my patients is currently 14 weeks pregnant. She is a teacher in grade 1, and there is an epidemic of Fifth disease in the school where she teaches. Can this disease affect her pregnancy and how should I care for her? ANSWER: Erythema infectiosum (Fifth disease) is usually a benign disease for children and mothers, but might have serious consequences for a fetus due to hemolytic anemia, although the risk is very low. You should evaluate the mother's immune status. If she is already immune (IgG positive), the risks are nil. If she is not immune (although the risk of the fetus's being affected is very low), fetal surveillance by repeated ultrasonographic examination and immune status reevaluation has been recommended. If a fetus is found to be affected, intrauterine evaluation and treatment are available at tertiary care centres.
The protective effect of ABO incompatibility between mother and fetus in respect of pregnancy-induced Rh isoimmunization has been recognized for approximately 20 years. Many have tacitly assumed that this protection was absolute and that when an infant was born with Rh hemolytic disease of the newborn, who was also ABO-incompatible with its mother, there must have been a previous ABO-compatible pregnancy in which the mother was initially sensitized. It has also been assumed that pregnancy-induced Rh isoimmunization could not occur if the father was AB and the mother O. Data are presented to show that both of these assumptions are not universally true. In a detailed study of a large number of families with pregnancy-induced Rh iso-immunization, nine families were found in which sensitization occurred and in which ABO incompatibility was present in every pregnancy. In addition, three families are documented in which pregnancy-induced Rh immunization had occurred and in which the father was AB and the mother O.
Alloimmunization against the Rhesus-D (RhD) antigen still remains as a major cause of hemolytic disease of fetus and newborn (HDFN). Determination of paternal RhDzygosity is performed by molecular testing and is valuable for the management of alloimmunized pregnant women. A 30-year-old pregnant woman with AB negative blood group presented with two consecutive abortions and no history of blood transfusion. By application of the antibody screening, identification panel, and selected cells, she was found to be highly alloimmunized. RhDzygosity was performed on her partner and was shown to be homozygous for RhD. The sequence- specific priming-polymerase chain reaction used in this report is essential to establish whether the mother requires an appropriate immunoprophylaxis or the fetus is at risk of HDFN.
Rhesus-Dzygosity; hemolytic disease of fetus and newborn; anti-D
California law, since January 1 1970, has required that all pregnant women, regardless of outcome of delivery, be tested for Rho(D) type, that the mother and physician be notified of the result and that hospitals providing service to newborns report all cases of Rho(D) Hemolytic Disease to the State Department of Public Health. Although there has been only a gradual decrease in the number of deaths due to Rho(D) Hemolytic Disease of the Newborn since 1950, there has been a precipitous fall in the past two years. Since the commencement of reporting of the disease to the State Health Department the number of cases has also dropped dramatically. It is felt that because of our conscientiously administered reporting law the morbidity and mortality figures from HDN in California are accurate, in contrast to results obtained in most other states.
It is believed that this report reflects the first really accurate look at a large population for the incidence and mortality from Rho(D) HDN since the advent of widespread use of anti-Rho(D) gamma globulin. Review of the recent literature failed to reveal definitive data on recent incidence and mortality trends for Rho(D) HDN. A survey of state health departments also failed to produce data comparable with California's.
A number of factors have played a part in reducing the incidence and mortality from Rho(D) HDN in California—namely, required testing of pregnant women combined with the almost routine use of of anti-Rho(D) immune globulin in eligible women, early recognition and treatment of Rho(D) HDN, and the reduction in family size with an increasing percentage of primiparous mothers.
The evolutionary history of variation in the human Rh blood group system, determined by variants in the RHD and RHCE genes, has long been an unresolved puzzle in human genetics. Prior to medical treatments and interventions developed in the last century, the D-positive children of D-negative women were at risk for hemolytic disease of the newborn, if the mother produced anti-D antibodies following sensitization to the blood of a previous D-positive child. Given the deleterious fitness consequences of this disease, the appreciable frequencies in European populations of the responsible RHD gene deletion variant (for example, 0.43 in our study) seem surprising. In this study, we used new molecular and genomic data generated from four HapMap population samples to test the idea that positive selection for an as-of-yet unknown fitness benefit of the RHD deletion may have offset the otherwise negative fitness effects of hemolytic disease of the newborn. We found no evidence that positive natural selection affected the frequency of the RHD deletion. Thus, the initial rise to intermediate frequency of the RHD deletion in European populations may simply be explained by genetic drift/ founder effect, or by an older or more complex sweep that we are insufficiently powered to detect. However, our simulations recapitulate previous findings that selection on the RHD deletion is frequency dependent, and weak or absent near 0.5. Therefore, once such a frequency was achieved, it could have been maintained by a relatively small amount of genetic drift. We unexpectedly observed evidence for positive selection on the C allele of RHCE in non-African populations (on chromosomes with intact copies of the RHD gene) in the form of an unusually high FST value and the high frequency of a single haplotype carrying the C allele. RhCE function is not well understood, but the C/c antigenic variant is clinically relevant and can result in hemolytic disease of the newborn, albeit much less commonly and severely than that related to the D-negative blood type. Therefore, the potential fitness benefits of the RHCE C allele are currently unknown but merit further exploration.
Blood group polymorphism; copy number variation; human evolution; balancing selection
The JAL antigen (Rh48) was discovered more than 30 years ago when it caused hemolytic disease of the fetus and newborn in an African American family. A decade later it was found to cause hemolytic disease of the fetus and newborn in a Caucasian family. The presence of the same low-prevalence antigen in two different ethnic groups is rare, but additional JAL+ in both groups was subsequently identified. This study was undertaken to investigate the RH gene(s) responsible for expression of JAL and to determine the structural relationship between JAL and other Rh antigens.
STUDY DESIGN AND METHODS
Samples from 17 JAL+ people were included: 2 Caucasian, 6 African American, 7 African Brazilian, 1 Caribbean, and 1 Puerto Rican. RHCE and RHD were investigated at the genomic level, and Rh cDNAs were cloned and sequenced for some samples.
Caucasian JAL+ probands had RHCE*Ce, while JAL+ probands with African ancestry had RHCE*ce, but all had a nucleotide 340C>T change in Exon 3 of RHCE predicted to encode Arg114Trp. The JAL-encoding RHCE*ce also had 733C>G (Leu245Val) and was linked to conventional RHD or to RHD*DAU0.
JAL+ results from a nucleotide 340C>T (Arg114Trp) on either a Ce or ce background. Homology modeling of the JAL+ RhCE protein suggests that the Arg→Trp change eliminates a critical loop-stabilizing H-bond between the side chain of Arg114 and the e-specific amino acid Ala226. Additionally, accommodation of the bulky tryptophan would disrupt the conformation of the extracellular loops containing C/c- and e-specific amino acids, providing a structural hypothesis for the simultaneous altered expression of C/c, e, and V/VS antigens.
Bovine neonatal pancytopenia (BNP) is a disease syndrome in newborn calves of up to four weeks of age, first observed in southern Germany in 2006. By now, cases have been reported in several countries around the globe. Many affected calves die within days due to multiple haemorrhages, thrombocytopenia, leukocytopenia and bone marrow depletion. A certain vaccine directed against Bovine Virus Diarrhoea Virus (BVDV) was recently shown to be associated with BNP pathogenesis. Immunized cows develop alloantibodies that are transferred to newborn calves via colostrum intake. In order to further elucidate BNP pathogenesis, the purpose of this study was to characterize and compare the protein composition of the associated vaccine to another vaccine directed against BVDV not related to BNP and the cell surface proteome of MDBK (Madin-Darby Bovine Kidney) cells, the cell line used for production of the associated vaccine.
By SDS-PAGE and mass spectrometry, we were able to detect several coagulation-related and immune modulatory proteins, as well as cellular and serum derived molecules being shared between the associated vaccine and MDBK cells. Furthermore, the number of proteins identified in the BNP related vaccine was almost as high as the number of surface proteins detected on MDBK cells and exceeded the amount of proteins identified in the non-BNP related vaccine over 3.5 fold. The great amount of shared cellular and serum derived proteins confirm that the BNP associated vaccine contained many molecules originating from MDBK cells and vaccine production.
The respective vaccine was not purified enough to prevent the development of alloantibodies. To narrow down possible candidate proteins, those most likely to represent a trigger for BNP pathogenesis are presented in this study, giving a fundament for further analysis in future research.
Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75). Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side.
Isoimmunization with anti-U antibody is a rare but significant cause of hemolytic disease in black newborns. In this case report, an lgG antibody stimulated by fetomaternal transfusion produced a positive direct Coombs' test on cord blood but not neonatal hyperbilirubinemia. A review of the literature suggests the pathophysiology is similar to Rh isoimmunization. The anti-U antibody may develop as a result of pregnancy or blood transfusion in the 1.2 percent of American blacks who are at risk for developing the antibody. The principles of treatment employed in Rh isoimmunization can be successfully used in isoimmunization due to anti-U.