[The anamnestic reaction in pregnant women isoimmunized to the Rh factor. (Description of 2 cases)].
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Fetal hematocrit values of blood obtained by percutaneous umbilical blood sampling were correlated with ultrasound findings in 35 samples from 15 pregnancies undergoing evaluation for Rh or Kell sensitization. Intravascular fetal transfusion was performed after a low hematocrit was obtained on 29 of 35 occasions. All fetuses with sonographic evidence of hydrops had a hematocrit of 15% or less, although three fetuses with hematocrits below 15% showed no signs of hydrops. In patients followed with serial sonography, hydramnios was noted as the earliest sonographic abnormality in six of nine pregnancies. All six fetuses were anemic (hematocrit 14-26%) and required transfusion. However, in three pregnancies where the fetus was anemic (hematocrit 22%), there was no hydramnios or other sonographic abnormality. Increased placental thickness was observed in association with fetal hydrops and a hematocrit below 15% in four cases, as well as in three other cases with fetal hematocrit between 16-29% but no fetal hydrops. Measurements of umbilical vein diameter provided no useful information because no increase was observed in these measurements, even in pregnancies with advanced fetal disease evidenced by hydrops.
Since immune memory in Rh(D)-negative isoimmunized subjects remains through life, even in the absence of measurable anti-Rh(D), we investigated the transformation of lymphocytes from such donors by Rh(D) antigen. The time lapse from the last stimulus was up to 13 years. Mononuclear cells from immunized women were stimulated by Rh(D)-positive erythrocyte stroma. Maximum transformation was observed on the sixth day of culture, with a stroma protein concentration of 8 micrograms/mL of culture medium. The stimulation index (SI) in cells from 11 immunized women was 6.8 +/- 3.1 (mean +/- SD), with a range from 3.1 to 15.0. In five different sets of control cultures, the SI ranged from 0.9 +/- 0.2 to 1.3 +/- 0.4. There was no overlap between stimulated and control cultures. No anti-D could be demonstrated in the serum of four of the 11 immunized cases studied. Also, transformation was observed in mononuclear cells from Rh(D)-negative immunized women with Rh(D)-positive erythrocytes. The findings demonstrate that lymphocytes from isoimmunized Rh(D)-negative subjects maintain the immune memory and are transformed in vitro by the Rh(D) isoantigen.
BACKGROUND: Rhesus (Rh) incompatibility is a cause of hemolytic disease of the fetus and newborn. Hemolytic disease results from the transplacentally transmitted maternal antibodies against Rh factor D and can cause permanent neurological damage in the affected newborn. This study examines the hypothesis that Rh incompatibility may be a risk factor for schizophrenia. METHODS: A sample of 1867 male subjects was divided into two groups, 535 Rh incompatible and 1332 Rh compatible, and compared on rate of schizophrenia. RESULTS: The rate of schizophrenia was significantly higher in the Rh-incompatible group (2.1%) compared with the Rh-compatible group (0.8%) (P < .03). In addition, since the risk for Rh hemolytic disease increases with second and later Rh incompatible pregnancies, it is noteworthy that the second- and later-born incompatible offspring exhibited a significantly higher rate of schizophrenia than second- and later-born compatible offspring (P < .05). Also, as predicted, the rate of schizophrenia among firstborn incompatible subjects was not significantly different from that of firstborn compatible subjects (1.1% vs 0.7%). CONCLUSION: Rh incompatibility may be a risk factor for schizophrenia.
This study reports our experience with 67 intrauterine transfusions (IUTs) carried out for 27 cases of severe Rh alloimmunization, which could be useful to other developing countries with similar situations. Most of the mothers were from sections of India other than Mumbai, their socioeconomic status was low, and they were referred during the second or third trimester. The mean gestation age at first IUT was 27+/-2.9 weeks and maternal anti-D titer ranged from 1:32 to 1:512. Ultrasonography (USG) was normal in eight cases, but showed minimal or gross ascites in 8 and 11 cases, respectively. The mean +/- SD hematocrit (HCT) in three groups defined by USG was 23.5+/-1.7, 15.9+/-4, and 12+/-5.9, respectively. Amniotic fluid analysis, which proved to be an important investigation, indicated IUT in eight cases having normal USG. Six cases were severely anemic (Hb deficit >7 g/dl). By fetal cell staining, the percentage of the donor's red cells in the fetal circulation was determined. Besides Hb, blood group, direct antiglobulin test, and mean cell volume, this parameter was also useful in assessing efficacy of IUT and the need for an exchange transfusion after birth. Of 11 fetuses having gross ascites, eight and one each from the remaining two groups, were stillborn. One death may be procedure related. Two neonates died due to hemorrhagic disorder and prematurity. The overall survival rate was 55.6%. Late referral, severe Rh alloimmunization, volume overload, delay in IUT because of nonavailability of blood and use of nonirradiated blood could be the reasons for the poor outcome. Strategies for improving results are discussed.
High homology, variant alleles, and silent alleles have made the development of completely reliable genotyping assays for the RHD and RHC alleles difficult. An RHD pseudogene (RHDPsi) possessing a 37-bp insertion within exon 4 is common among serologically RhD-negative individuals of African descent and generates false-positive results in previously reported RhD genotyping assays. Genotyping RhC is problematic due to exon 2 homology between RHD and RHC; however, an RHC-specific 109-bp insertion within intron 2 has been reported useful for genotyping. Primers flanking the exon 4 insertion point were used for detection of RHD and RHDPsi among a total of 231 serotyped individuals: 134 African American, 85 Caucasian, and 12 RhD serotype-negative/genotype-positive, D-sensitized women. Primers flanking the RHC-specific intron 2 insertion were used to genotype 282 serotyped individuals (128 African American, 154 Caucasian) and were compared to RHC genotyping using the exon 1 RhC-specific nt48 cytosine polymorphism. Complete correlation was observed between genotyping with the RHDPsi primer pair and serotyping among 219 individuals and 10/12 previous RHD false-positive genotyping results were resolved. RHDPsi was detected in 19% (n = 4/21) of RhD seronegative African Americans and 4.4% (n = 5/113) of RhD seropositive African Americans. When using the 109-bp intron 2 insertion for genotyping of RHC, a 23.9% (n = 11/46) false-negative rate was observed among African American RhCc serotyped heterozygotes. Utilization of the exon 1 nt48 cytosine for indirect genotyping of RHC yielded a 7.2% (n = 4/55) and 56.3% (n = 45/80) false-positive rate among Rhcc Caucasians and African Americans, respectively. We conclude that these additional reactions, though not sufficient alone, can be useful supplements to existing Rh genotyping assays.
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Although Rh immune globulin is commonly given to Rh-negative women undergoing genetic amniocentesis, there is little documentation of the necessity, efficacy, or safety of this policy. In this study, reproductive outcomes in 147 women each receiving 150 micrograms of Rh immune globulin after genetic amniocentesis were compared with those of an equal number of Rh-positive amniocentesis control women. No significant differences were found in the incidence of midtrimester pregnancy loss, mean gestational age at delivery, mean birth weight, or frequency of preterm deliveries (P greater than 0.05 for all parameters). While two antepartum stillbirths occurred in the study group and none in the control population, causes unrelated to Rh immune globulin administration were apparent for both fetal deaths (one multiple congenital anomaly syndrome, one abruptio placentae at 38 weeks). Of the 103 Rh-negative women giving birth to Rh-positive infants, none were overtly sensitized at the time of delivery. It is concluded that second trimester Rh immune globulin administration does not increase the risk of pregnancy loss.
In 944 Rh-negative patients who received rhesus immunoglobulin (anti-D) following genetic amniocentesis, not a single case of Rh sensitization occurred. Routine administration of a small dose (100 micrograms) of anti-D is effective in preventing Rh sensitization after midtrimester amniocentesis.
BACKGROUND: In this prospective study, we assessed the feasibility of fetal RH genotyping by analysis of DNA extracted from maternal plasma samples of alloimmunized pregnant women using real-time PCR and primers and probes targeted toward RHD (exon 7 and exon 10) and RHCE (intron 2 and exon 5) genes. METHODS: We analysed 23 alloimmunized pregnant women (16 anti-D, 5 anti-D + C, 2 anti-E) at risk of haemolytic disease of the newborn (HDN) within 11th and 37th week of pregnancy and correlated the results with serological analysis of cord blood. RESULTS AND CONCLUSION: Detection of the presence of the RHD gene, the C and/or E alleles of the RHCE gene in maternal plasma samples is highly accurate and enables implementation in a clinical diagnostic algorithm for following pregnancies at risk for HDN. The absence of RHD gene, the C and/or E alleles of RHCE gene in the current pregnancy excludes the risk of HDN caused by anti-D, anti-C and/or anti-E alloantibodies and the performance of invasive fetal-blood sampling.
The hypothesis that the Rh and ABO blood systems behave like the HLA system in relation to mother-conception tolerance-rejection mechanisms was tested in 25,501 mother-infant pairs. According to this hypothesis, heterozygotes carrying a paternal gene that is not present in their mothers should be better tolerated than homozygotes. Significantly more BO infants born to AO mothers. AO infants born to BO mothers, Rh(+) heterozygotes born to Rh(-) mothers, and less significantly AO infants born to OO mothers confirm the hypothesis. Fewer homozygotes occurred in Rh(-) infants born to Rh(+) mothers and in O infants born to non-O mothers. Deviations from the Hardy-Weinberg equilibrium found in the ABO system were modified by the Rh and sex of the infant. These data strongly support the hypothesis that at least two feto-maternal systems influence the destiny of pregnancies: the classical known incompatibility system which operates late in pregnancy and a new one which is based on the induction of maternal tolerance early in pregnancy: maternal tolerance seems to be better elicited by heterozygous eggs or embryos carrying a gene not present in the mother. The data also support the hypothesis that the sex ratio is influenced by feto-maternal tolerance-rejection mechanisms associated with the ABO and Rh systems.
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Monoclonal antibodies to D antigen were studied in the reaction of antibody-dependent cytotoxicity for evaluation of the possibility of using these antibodies for preventing rhesus sensitization. High hemolytic activity of four anti-D-monoclonal antibodies in the antibody-dependent cytotoxicity test, mediated by their interaction with FcgammaRI, and the capacity to accelerate elimination of D+ erythrocytes from circulation did not provide the immunosuppressive effect. It was hypothesized that monoclonal antibodies for prevention of rhesus sensitization should interact with FcgammaRIII on lymphocytes. These monoclonal antibodies are extremely rare: only 4 of 125 studied antibodies mediated hemolysis in the antibody-dependent cytotoxicity test with lymphocytes, while all polyclonal anti-D-preparations exhibited this activity.