Search PubMed⌕ Search

Biomedical subjects

M A Overbeeke

Publications and source records attributed to M A Overbeeke.

At least 19 recordsLinked to original sources
PubMed2001

Intravascular hemolysis by IgA red cell autoantibodies.

A 66-year-old male patient with severe intravascular hemolysis is presented. Laboratory investigation revealed initially a negative direct antiglobulin test (DAT), suggesting a Coombs-negative hemolytic anemia. Additional testing with monospecific anti-IgA was strongly positive. IgA autoantibodies with anti-e specificity and nonspecific IgA autoantibodies were identified. A diagnosis of IgA-only-associated warm AIHA was made. Treatment included transfusion of multiple e-negative typed red cell concentrates and administration of high-dose prednisone. The pathophysiologic mechanism of the rare IgA-induced warm AIHA is discussed.

Aged↗
PubMed2001

Clinical value of an antibody-dependent cell-mediated cytotoxicity assay in the management of Rh D alloimmunization.

OBJECTIVE: The aim of this study was to evaluate the clinical value of an antibody-dependent cell-mediated cytotoxicity assay relative to the indirect antiglobulin test titer in the management of Rh D-alloimmunized pregnancies. STUDY DESIGN: Data from 172 Rh D-alloimmunized pregnancies were analyzed retrospectively. The accuracies of the highest antibody titer and of the highest antibody-dependent cell-mediated cytotoxicity assay result during pregnancy to predict fetal and neonatal Rh disease, defined as the need for intrauterine (n = 30) or neonatal (n = 37) blood transfusion, respectively, were assessed. RESULTS: At different cutoff levels with equal sensitivities the antibody-dependent cell-mediated cytotoxicity assay consistently showed a higher specificity than the antibody titer for the prediction of fetal disease. No difference was found between the receiver operating characteristic curves of the 2 tests for the prediction of neonatal disease. CONCLUSIONS: Selection of patients for referral and invasive testing for Rh D alloimmunization may be improved with the use of an antibody-dependent cell-mediated cytotoxicity assay.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1999

[Prenatal typing of Rh- and Kell- blood group system antigens].

Rhesus (Rh) and Kell blood group immunisations are the most frequent causes of haemolytic disease of the newborn. Recently, the molecular bases of the Rh and Kell antigens have been elucidated. Subsequently, specific polymerase chain reactions (PCRs) could be developed to determine the RhD, RhC/Rhc and RhE/Rhe genotypes as well as the KI genotype (from the Kell blood group) with genomic DNA. The tests were applied to genomically determine the foetal Rh and Kell blood groups with DNA obtained from amniotic fluid cells. The genotypes obtained were compared with the Rh phenotypes established by cord blood red cell serology. The PCRs to determine the RhD, Rhc, RhE and Rhe and KI genotypes were found to be reliable. The test for RhC however, resulted in false-positive C genotypes. Indeed, more than half of the subsequently tested C-negative Negroid donors were false-positive with the DNA test. Thus, except for RhC, it is possible to reliably determine the Rh and KI genotypes of a foetus with DNA isolated from amniotic fluid cells. Amniocentesis, however, carries a risk for the pregnancy and therefore the tests will only be justified in pregnant women in whom an antibody has been detected and the father of the foetus is heterozygous for the specific antigen. Recently foetal RhD genotypes were determined in foetal DNA circulating in the plasma of RhD-negative pregnant women. This could eventually lead to the introduction of assays with which the foetal blood group can be determined without any risk to the foetus.

Adult↗
PubMed1999

[Two neonates with severe rhesus antagonism inspite of low values in recent tests of antibody dependent cellular cytotoxicity (ADCC)].

In two female newborn babies severe haemolytic disease of the newborn developed due to anti-RhD antibodies of the mother. In both cases the results of the last antibody-dependent cellular cytotoxicity (ADCC) test had been < 10% (two and three weeks before parturition respectively) making haemolytic disease unlikely. The ADCC test is used to determine the destructive power of the responsible maternal antibodies. It is believed that with a low ADCC value (< 10%), there is no danger of clinically relevant haemolytic disease. The first neonate recovered after exchange transfusion, the second died notwithstanding extensive supportive therapy. A recent low ADCC value makes serious haemolytic disease unlikely, but does not completely exclude it, as the titre of the causative antibodies can rise very quickly.

Adult↗
PubMed1999

[Hemolytic disease of the newborn and irregular blood group antibodies in the Netherlands: prevalence and morbidity].

OBJECTIVE: To inventory prevalence and morbidity of haemolytic disease of newborn caused by irregular anti-erythrocyte antibodies other than antirhesus-D. DESIGN: Prospective registration study. METHOD: All paediatricians (n = 380) in general hospitals and contact persons (n = 79) in university hospitals were asked for monthly reports of clinical cases of haemolytic disease of newborn during 2 years (1996-1997). RESULTS: Response was 97%. A total of 130 reports were received in two study years, 49 of which could not be confirmed as non-RhD-non-AB0 antagonism. In the group of which the transfusion history was known (n = 60), 29 pregnant women (48%) had received transfused blood at some time. Of the antibodies found, anti-c, anti-E and anti-K were the most frequent. The direct antiglobulin test was positive in 61 of the 81 cases, negative in 10 cases, while in 10 cases it was unknown or false-negative due to earlier intrauterine transfusions (in three neonates). The highest bilirubin levels recorded were 572, 559 and 520 mumol/l (all three with maternal anti-c antagonism). Therapeutic data were known concerning 80 of the 81 newborn: 21 (16%) received no treatment, 24 (29%) only phototherapy and the others--in addition to phototherapy if any--also blood transfusion, exchange transfusion or intrauterine transfusion, or a combination of these. CONCLUSION: It was calculated that the actual prevalence of irregular anti-erythrocyte antibodies in Dutch pregnant women probably amounts to approximately 0.25%. This finding may possibly be confirmed since starting 1 July 1998 all pregnant women in the country are screened for the presence of these antibodies. It is recommended that girls and women in the reproductive age group should receive primary prevention of development of irregular anti-erythrocyte antibodies by application of a selective blood transfusion policy, taking into account the occurrence of the antigens c, E and K.

Blood Group Incompatibility↗
PubMed1999

Glycophorin A mutation Ala65 --> Pro gives rise to a novel pair of MNS alleles ENEP (MNS39) and HAG (MNS41) and altered Wrb expression: direct evidence for GPA/band 3 interaction necessary for normal Wrb expression.

We report here a novel Glycophorin A (GPA) mutation Ala65 --> Pro which gives rise to a low-incidence antigen HAG, lack of a high-incidence antigen ENEP and aberrant expression of the high-incidence Wrb antigen. Anti-ENEP was identified in the serum of a transfused male patient (E.H.) who was homozygous for a GPA Ala65 --> Pro mutation and possessed a novel low-incidence antigen which we have called HAG. An unrelated HAG-positive individual, heterozygous for the Ala65 --> Pro mutation, has also been identified. Anti-HAG was present in several multispecific antisera to low-incidence antigens and in one monospecific serum. Normal expression of the Wrb antigen depends on the presence of amino acid Glu658 of band 3 and on the presence of GPA. However, a specific epitope on GPA has not previously been implicated. DNA sequence analysis of band 3 from patient E.H. was normal in the region of Wra/Wrb polymorphism with homozygous presence of Glu658 and therefore the abnormal Wrb expression results from the Ala65 --> Pro mutation in GPA. The ENEP and HAG antigens have been assigned the MNS blood group system numbers 002.039 and 002.041, respectively, by the ISBT Working Party on Terminology for Red Cell Surface Antigens.

Alanine↗
PubMed1998

The diagnostic value of thrombopoietin level measurements in thrombocytopenia.

It has been reported that blood trombopoietin (TPO) levels can discriminate between thrombocytopenia due to increased platelet destruction and decreased platelet production. With our TPO ELISA and a glycocalicin ELISA we analysed a large group of patients in detail and could confirm and amplify the above notion in detail. TPO levels were determined in plasma from 178 clinically and serologically well-defined thrombocytopenic patients: 72 patients with idiopathic autoimmune thrombocytopenia (AITP), 29 patients with secondary AITP, 5 patients with amegakaryocytic thrombocytopenia and 72 patients who suffered from various diseases (46 in whom megakaryocyte deficiency was not and 26 in whom it was expected). In addition, we measured the level of glycocalicin as a marker of total body mass of platelets. In all patients with primary AITP and secondary AITP, TPO levels were within the normal range or in some (n = 7) cases only slightly increased. The level of glycocalicin was not significantly different from that of the controls (n = 95). The patients with amegakaryocytic thrombocytopenia had strongly elevated TPO levels and significantly decreased glycocalicin levels. Similarly, among the 72 thrombocytopenic patients with various disorders, elevated TPO levels were only found in patients in whom platelet production was depressed. The mean level of glycocalicin in these patients was decreased compared to that in controls and patients with AITP, but was not as low as in patients with amegakaryocytic thrombocytopenia. In conclusion, all patients with depressed platelet production had elevated levels of circulating TPO, whereas the TPO levels in patients with an immune-mediated thrombocytopenia were mostly within the normal range. Therefore, measurement of plasma TPO levels provides valuable diagnostic information for the analysis of thrombocytopenia in general. Moreover, treatment with TPO may be an option in AITP.

Adolescent↗
PubMed1997

[Linguistics in blood group serology].

With a view to terminological uniformity, blood group serologists, immunologists and transfusion physicians should refer only to the "ABo' (zero) in stead of the "ABO' system. They also should use "HLA antibodies' in stead of "anti HLA antibodies'. The new Dutch spelling "resus' in stead of "Rhesus' is incorrect from a historical point of view.

Blood Group Antigens↗
PubMed1997

Molecular background of VS and weak C expression in blacks.

BACKGROUND: The Rh system is complex and consists of as many as 45 different antigens. Red cells of about 25 percent of the black population carry VS an Rh-system antigen (Rh20), but this antigen is very rare in whites. VS positivity is always associated with a weak expression of e, and usually also of C. STUDY DESIGN AND METHODS: The RH genes of 11 black VS-positive donors were studied. Transcripts were sequenced for four VS-positive donors, three of whom had red cells with a weak expression of C. In the other donors, only analysis of genomic DNA was carried out. RESULTS: The occurrence of VS was shown to be related to a single-point mutation in exon 5 of the RHCE gene (cytosine 733 guanine, leading to the Leu245Val substitution). The presence of this polymorphism in exon 5 may explain the simultaneously occurring weak e, because the E/e polymorphism is located in the same exon. Study of VS-positive donors with different Rh phenotypes showed that the polymorphism can occur in different alleles of the RHCE gene. In all three donors whose red cells showed a weak expression of C, a hybrid D-CE-D transcript was found, containing exon 4, 5, 6, 7, and (probably) 8 from the RHCE gene. No transcripts were encountered carrying DNA markers normally associated with C expression. CONCLUSION: It is therefore postulated that the hybrid gene is responsible for the weak expression of C in these individuals. The hybrid gene carried a Leu62Phe substitution, as well as the Leu245Val substitution responsible for VS. The gene most probably cosegregates with a C allele encoding Cys 16 (normally encoded only by the C allele) and Val245 (responsible for VS antigenicity when encoded by the RHCE gene). This explains the combination of weak expression of C and VS positivity that is frequently found in blacks.

Africa, Northern↗
PubMed1997

Lower antigen site density and weak D immunogenicity cannot be explained by structural genomic abnormalities or regulatory defects of the RHD gene.

BACKGROUND: The weak D phenotype is characterized serologically by a weak or negative agglutination reaction with polyclonal anti-D in an immediate-spin test. Agglutination is enhanced in the indirect antiglobulin test. Red cells that are typed weak D have a much lower number of apparently complete D antigens at their cell surface and are associated with considerably weaker immunogenicity than are red cells with normal D. In a previous study, the number of D sites per cell was determined in eight unrelated weak D individuals to range from 490 to 1870 D sites per cell, which corresponded to 4 to 14.2 percent of the number of D sites in CcDee samples. STUDY DESIGN AND METHODS: The RHD gene was investigated for structural abnormalities by Southern blot experiments and polymerase chain reaction-based RHD typing in these individuals. In addition, abnormalities in the transcription process were studied by sequence analysis of RH transcripts and by comparing the relative amounts of RHD mRNA in weak D to those in CcDee, CcDEe, and -D- samples by using a semiquantitative reverse transcriptase-polymerase chain reaction analysis. RESULTS: The RHD gene in weak D phenotypes does not show any abnormalities at either the genomic or the transcriptional level when compared to the RHD gene in normal D phenotypes. CONCLUSION: The weaker immunogenicity of weak D is not explained by structural difference in the RHD gene itself. The weaker expression of D might be caused by factors involved in the Rh-related complex or by an as yet unidentified suppressor gene. This study supports the concept that weak D phenotypes carry complete D polypeptides and reflect a quantitative rather than a qualitative variation of D.

Antibodies, Monoclonal↗
PubMed1996

Rh DNA analysis.

Explore the source record for details and available documents.

Humans↗
PubMed1996

The R0Har RH:33 phenotype results from substitution of exon 5 of the RHCE gene by the corresponding exon of the RHD gene.

The highly polymorphic Rh (Rhesus) system is encoded by two homologous genes, one encoding the D polypeptide and the other the CcEe polypeptides. Partial D antigens may be caused by gene rearrangements, deletions or point mutations. In this study the molecular basis of R0Har RH:33, a Rh phenotype of low frequency, is described. The R0Har RH:33 phenotype is characterized by partial expression of D, altered expression of e, absence of G and the presence of two antigens of low frequency: Rh33 and FPTT. Southern blot analysis, RHD typing by PCR and sequence analysis of Rh transcripts revealed that the RHD gene is absent in subjects with this phenotype. Apart from the expected RHCE transcripts, a new Rh transcript, RHc(D)(e), was identified in three unrelated individuals expressing R0Har Rh:33. The RHc(D)(e) transcript showed the same sequence as the RHce transcript, with the exception of exon 5, which was substituted by the corresponding exon of the RHD gene. A method for PCR-based genotyping was developed to determine specifically the c(D)(e) haplotype. The c(D)(e) PCR proved to be a reliable alternative method for R0Har RH:33 typing.

Base Sequence↗
PubMed1996

The genetic basis of a new partial D antigen: DDBT.

The Rh system, the most polymorphic system on red cells, is genetically controlled by two different but highly homologous genes on chromosome 1. The RHCE gene encodes different RhCcEe polypeptides and the RHD gene encodes D antigens. It is well established that in D negative individuals the RHD gene is either absent or grossly deleted. The D antigen comprises at least nine serologically defined D epitopes. The D antigen can be divided into different partial D categories, reflecting a different pattern of specific D epitopes. In this study a newly defined partial D antigen, DDBT, was studied. D epitope mapping revealed the presence of D epitopes 6/7 and 8 and the absence of the other D epitopes. The molecular basis of this phenotype was studied by Southern blotting, by RHD typing using the polymerase chain reaction (RHD-PCR) and by sequence analysis of Rh transcripts. The DBT phenotype appeared to be encoded by a hybrid RHD gene, in which exons 5, 6 and 7 (and possibly the identical exon 8) were replaced by the corresponding exons of the RHCE gene. From this study it may be concluded that D epitopes 1, 2, 3, 4, 5 and 9 are dependent on the presence of RHD exons 5, 6, and 7.

Base Sequence↗
PubMed1996

A new low-incidence antigen in the Kell blood group system: VLAN (KEL25).

A multilaboratory investigation has identified a new low-incidence antigen "VLAN' on the red cells of a blood donor. The VLAN antigen is destroyed by 2-aminoethylisothiouronium bromide treatment of the donor's red cells suggesting an association with the Kell system. Monoclonal antibody-specific immobilization of erythrocyte antigen analysis with anti-VLAN and with several mouse monoclonal antibodies directed at epitopes on the Kell glycoprotein gave positive results, indicating that the VLAN antigen is located on the Kell glycoprotein. The VLAN red blood cells have the common Kell phenotype: KEL:-1,2,-3,4,5,-6,7,-10,11,12,13,14,-17,18,19,-21,22,-23,-24. Additional serologic data indicate that the VLAN antigen is not part of any other ISBT blood group system, collection or series. A family study showed that the VLAN antigen is inherited since the red cells of two sisters and one niece of the propositus are also VLAN+. The ISBT Working Party on Terminology for Red Cell Surface Antigens has assigned VLAN to the Kell blood group system as KEL25 (number for computer listings 006025).

Antigens↗
PubMed1996

The RoHar antigenic complex is associated with a limited number of D epitopes and alloanti-D production: a study of three unrelated persons and their families.

BACKGROUND: the RoHar antigenic complex has been characterized serologically by difficulties in D typing, weak e expression, lack of G antigen, presence of Rh33, a low-frequency Rh antigen, and, more recently, a second low-frequency antigen, FPTT. Allocation to one of the partial D catagories was not considered because of the unuaual reactions of RoHar cells and because anti-D production was not observed in RoHar persons. STUDY DESIGN AND METHODS: Three unrelated RoHar donors and their families were studied in detail with special emphasis on D epitope mapping, e and G typing, and screening for antibodies. RESULTS: Only D epitopes 5 and 6/7 were demonstrable, and D epitopes 1, 2, 3, 4, 8, and 9 seem to be absent in the RoHar complex. In one individual, the presence of alloanti-D with limited specificity, not reacting with RoHar red cells of other individuals, was found 6 months after a second D+ pregnancy. CONCLUSION: The finding of alloanti-D in an RoHar r person supports the concept that the D characteristic of this phenotype is a partial D antigen, which is consistent with the presence of the limited number of D epitopes found in epitope mapping. As has been suggested for other partial D antigens, RoHar individuals should be regarded as D- for the receipt of blood, and pregnant RoHar women who have had D+ pregnancies should receive anti-D prophylaxis.

Epitopes↗