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V Kiefel

Publications and source records attributed to V Kiefel.

At least 91 records · Page 5Linked to original sources
PubMed1991

Autoantibodies against platelet glycoprotein Ib/IX: a frequent finding in autoimmune thrombocytopenic purpura.

Many autoantibodies involved in the pathogenesis of autoimmune thrombocytopenic purpura (AITP) are directed against epitopes on platelet glycoproteins (GP). These autoantibodies are a specific diagnostic characteristic of patients with AITP. In this study, the relative frequency of antibodies against GPs IIb/IIIa and Ib/IX was assessed in sera from 81 AITP patients with a glycoprotein-specific enzyme immunoassay (MAIPA assay) using monoclonal antibodies against these platelet GPs. All sera contained platelet-specific antibodies which had been detected by platelet immunofluorescence. Of the 81 antibodies tested, 58 (72%) reacted with at least one of the platelet GPs studied. Autoantibodies against GPIb/IX were as common as antibodies against the GPIIb/IIIa complex. The same ratio of specificities was observed on autologous platelets of an independent cohort of 29 patients. The epitope of three autoantibodies against GPIb/IX and of mab Gi10, a monoclonal antibody, which inhibits binding of these autoantibodies, was further characterized. Severity of thrombocytopenia was not related to the GP specificity of the autoantibody. The observation that in 23 (28%) of these sera the antigenic determinants could not be assigned to the glycoproteins under investigation suggests that platelet autoantibodies may react with other GPs or other membrane constituents, e.g. glycolipids.

Antibodies, Monoclonal↗
PubMed1991

High-dose intravenous gammaglobulin for neonatal alloimmune thrombocytopenia in twins.

We report the successful treatment of neonatal alloimmune thrombocytopenia with repeated infusions of high-dose immunoglobulin G (400 mg/kg/d for 5 days) in twins. Platelet counts increased within 3 days from less than 20 x 10(9)/l to more than 70 x 10(9)/l. The first twin survived without neurological or other sequelae. The second twin had probably developed intracranial hemorrhage (ICH) in utero. This infant developed long-term neurological sequelae with blindness, cerebral palsy and infantile spasms. Implications of the therapeutic approach and prevention of severe complications in pregnancies with known risk for neonatal alloimmune thrombocytopenia are discussed.

Autoimmune Diseases↗
PubMed1990

Sra, a private platelet antigen on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia.

A new platelet alloantigen, Sra, is described that was defined by an alloantibody detected in the serum of a healthy mother who delivered a child with typical clinical signs of neonatal alloimmune thrombocytopenia (NAIT). The antibody reacted strongly with the child's and father's platelets, but not with platelets of the mother or with those of a highly selected panel representing all known platelet alloantigens. Platelets from 300 unselected normal blood donors also tested negative, suggesting a phenotype frequency in the German population of less than 0.01. The antigen was present in 9 of 20 members within three generations of the paternal family, indicating autosomal codominant inheritance. By immunochemical analysis using a glycoprotein (GP)-specific immunoassay and a variety of GP IIb/IIIa-specific monoclonal antibodies for antigen immobilization (MAIPA assay), radioimmunoassay, and Western blotting, we could show that the antigen resides on a 68-Kd proteolytic fragment of GP IIIa. Immunogenetic data and gene dosage studies revealed that the Sra antigen is not related to any of the other known platelet alloantigens. In accordance with established criteria, the Sra antigen represents the first example of a "private" platelet alloantigen that bears significance in rare instances of NAIT.

Adult↗
PubMed1990

Impaired agglutination of IgM resulting from non-enzymatic glycation in diabetes mellitus.

Non-enzymatic glycation of circulating immunoglobulin G, A and M, measured by boronic acid affinity chromatography was found to be significantly increased in diabetes mellitus. The mean value of glycated IgM was already high in the control group: 49.58% (+/- 10.3% SD) and increased up to a mean value of 61.00% (+/- 8.5%) in the diabetic group. Similarly IgG and IgA glycation was significantly higher in the diabetic group than in controls: IgG 21.6% (+/- 3.4%) vs. 14.1% (+/- 2.9%; P less than 0.01); IgA 14.7% (+/- 4.9%) vs. 7.7% (+/- 1.3%; P less than 0.01). To investigate how glycation would alter IgM function, serum proportions from diabetic patients with blood group O were separated into glycated and non-glycated fractions by affinity chromatography and, adjusted to the same concentrations, tested against group A1 erythrocytes. Agglutination, which is mainly an IgM-mediated reaction, was significantly lower in the glycated than in the non-glycated fraction of IgM. The correlation between glycation of IgM and the reduction of agglutination titres in the glycated fraction was significant (r = 0.88, P less than 0.001). We conclude that impaired IgM function may be caused by non-enzymatic glycation in diabetes mellitus with possible consequences for host resistance in the early phase of infection.

Agglutination↗
PubMed1990

Incidence and specificity of HLA-DP antibodies in pregnancy sera.

A total of 630 human pregnancy sera were investigated for HLA-DP antibodies (ab) by monoclonal antibody-specific immobilization of leukocyte antigens (MAILA) using monoclonal antibody (mAB) B7/21.2 and selected B-lymphoblastoid cell lines from the Tenth International Histocompatibility Workshop reference panel. DP-specific abs were detected in 86 of 330 sera (26.1%) of a retrospective series selected for positive reactions in lymphocytotoxicity screening, and in 29 of 300 unselected sera (9.7%) of a prospective series. Approximately 80% of DP-reactive sera were also positive in lymphocytotoxicity test for class I and/or class II ab. On the other hand, sera containing lymphocytotoxic ab for both class I and class II ab revealed the highest incidence of DP ab (35%). Out of 115 DP-reactive sera, 28 clearly presented one or more DP specificities. Absorption/elution studies revealed complex patterns of reactivity in some sera which were similar to those of known mABs and possibly reflect supertypic DP specificities and/or serological cross-reactions. Serological DP typing of individuals by the MAILA technique appears promising.

Antibodies, Monoclonal↗
PubMed1990

The platelet glycoprotein Ia-IIa-associated Br-alloantigen system is expressed by cultured endothelial cells.

To obtain information on the immunological relationship between the endothelial and platelet glycoprotein (GP)Ia-IIa (VLA-2) complex, we studied whether endothelial GPIa-IIa was able to express the platelet GPIa-IIa-associated Br-alloantigen system. Therefore, we tested antisera to both allelic forms of the Br system (Bra and Brb) on platelets (by an assay based on monoclonal antibody-specific immobilization of platelet antigens, MAIPA) and on cultured umbilical vein endothelial cells (by immunoprecipitation experiments) from the same individual. Endothelial cells from a platelet Br(a + b +), and from a platelet Br(a - b +) individual were studied. Our results indicate that endothelial GPIa-IIa is indistinguishable from platelet GPIa-IIa in its ability to express the Bra and Brb alloantigens. The association of Br alloantigens with endothelial GPIa-IIa was confirmed by the results of an assay based on monoclonal antibody-specific immobilization of endothelial antigens (MAIEA). These data further illustrate the structural and immunologic similarity of platelet and endothelial cell GPIa-IIa (VLA-2).

Alleles↗
PubMed1990

[Comparison of 4 crossmatching methods for predicting the success of platelet transfusion].

Long term platelet transfusion support often results in alloimmunization of the recipients and refractoriness to further platelet transfusions. Crossmatch tests between the recipients' serum and the donor platelets offer a potential solution to this problem. In the present study, 207 donor-recipient pairs were studied in 65 patients. We compared four assays (LCT, PAIFT, ELISA and MAIPA) in their ability to predict the response in patients receiving multiple platelet transfusions. All four techniques showed a similar predictability of transfusion outcome (79-80%). Of the four assays, the LCT had the highest specificity (100%) and the PAIFT had the highest sensitivity (70%). In comparison to the three other techniques, the MAIPA assay, a glycoproteinspecific immunoassay, offers the possibility to distinguish between HLA-specific (cytotoxic and noncytotoxic) and platelet-specific antibodies in the same serum specimens. Our results demonstrate that HLA antibodies are the major cause of platelet transfusion refractoriness. Platelet specific (i.e. anti-Zwb) and ABO antibodies are involved in approximately 10%.

Adolescent↗
PubMed1990

[The Br(a)/Br(b) alloantigen system in thrombocytes].

Platelet specific alloantibodies cause neonatal alloimmune thrombocytopenia (NAIT), posttransfusion purpura (PTP) and may be found in patients who are refractory to HLA-matched platelet transfusion. Most platelet alloantigen systems comprise two alleles: Zw(a)/Zw(b), Ko(a)/Ko(b), Bak(a)/Bak(b), Yuk(a)/Yuk/b). The corresponding antibodies are detected with the platelet immunofluorescence test, radioimmunoprecipitation, immunoblot, and with a glycoprotein-specific immunoassay. Epitopes of the Zw-, Bak-, and Yuk-alloantigen systems are localized on the GPIIb/IIIa complex. Recently, we characterized antibodies against two alleles of a new alloantigen system (Bra/Brb). Anti-Bra is the second most important antibody to cause NAIT, following Anti-Zwa. Anti-Brb was found in three polytransfused patients. The Br-antibodies may be detected using a glycoprotein-specific enzyme immunoassay (MAIPA assay) and radioimmunoprecipitation. The frequency of the Br-phenotypes in our population is Br(a+b-) 1%, Br(a+b+) 20%, Br(a-b+) 79%. The number of binding sites for Anti-Bra is 2000/platelet on homozygous and 1000/platelet on heterozygous platelets. The Br-alloantigens are localized on GPIa, which is identical with the alpha chain of VLA-2 on activated T-lymphocytes.

Antigens, Human Platelet↗
PubMed1990

[Sr(a), a "private" thrombocyte alloantigen as a cause of neonatal alloimmune thrombocytopenia].

Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal immunization against fetal platelet antigens. In the serum of a mother who gave birth to a child with the typical clinical picture of NAIT we found an antibody directed against the new platelet antigen Sra. Anti-Sra was found to react in the immunofluorescence test and in a glycoprotein (GP) specific immunoassay (MAIPA) using a monoclonal antibody against GP IIb/IIIa for antigen immobilization with the child's and father's platelets. Radioimmunoprecipitation and immunoblot allowed to assign the Sra-antigen to GP IIIa. The phenotype frequency was estimated less than 1%, characterising the Sra-antigen as the first 'private' alloantigen on platelets.

Blood Platelets↗
PubMed1990

[Serologic characterization of platelet-associated IgG and its significance for the diagnosis of thrombocytopenias].

Detection of platelet autoantibodies in patients with autoimmune thrombocytopenic purpura (AITP) is a notoriously difficult task. The quantitative measurement of PAIgG is rather unreliable as a diagnostic procedure because it tends to yield false positive results in thrombocytopenic patients. In this study two different techniques allowing discrimination of platelet autoantibodies and unspecific IgG bound to the patients' autologous platelets were compared to the quantitative measurement of PAIgG in thrombocytopenic patients. These two techniques are: 1. investigation in the platelet adhesion immunofluorescence test of eluates prepared from the patients' platelets and 2. detection of platelet autoantibodies on the isolated glycoprotein complexes IIb/IIIa, Ib/IX, and Ia/IIa. Results show that positive results with these two techniques are much more specific for autoimmune thrombocytopenia than elevated amounts of PAIgG measured on whole platelets.

Autoimmune Diseases↗
PubMed1990

[219 Zw(a) positive mothers of children with clinically suspected neonatal alloimmune thrombocytopenia].

The sera of 219 Zwa-positive mothers who gave birth to children with clinically suspected neonatal alloimmune thrombocytopenia (NAIT) were tested for platelet-reactive antibodies using the platelet adhesion immunofluorescence test and a glycoprotein-specific immunoassay (MAIPA). In 102 families a serological crossmatch of maternal serum against paternal platelets was performed. 12 sera contained platelet specific antibodies: Zwb (1), Bra (4), Bra and HLA (5), Baka and HLA (1), Sra (1); three further sera contained antibodies against blood group A (1), blood group B (1), blood group B and HLA (1). Anti-Bra was the most important antibody in this cohort. There is evidence that in certain cases antibodies against blood group antigens A or B may cause NAIT. Clinical data of NAIT duo to anti-Bra suggest a less severe bleeding tendency than in NAIT due to anti-Zwa. The HLA-DRw6 antigen was identified as an immunogenetic marker for the immunization against the Bra-antigen.

Antibody Specificity↗
PubMed1989

348 cases of suspected neonatal alloimmune thrombocytopenia.

Serological and clinical data were collected in 348 cases of suspected neonatal alloimmune thrombocytopenia (NAT). Of the 144 mothers who were Zwa-negative, 107 had Zwa antibodies--alone (94); with HLA antibodies (12); or with Bra antibodies (1). Antibodies were detected in 12 of the 204 Zwa-positive mothers as follows: anti-Bra (9), anti-Zwb (1), anti-Baka with HLA antibody (1), and blood group B isoagglutinins (1). The frequency of NAT due to Bra incompatibility (19%) was second to Zwa (78%). Zwa-NAT was clinically the more severe (14% had intracranial haemorrhages) and responded well to either maternal platelet transfusions or intravenous IgG. In Bra-NAT intracranial haemorrhages were not observed and most children recovered without specific therapy.

Adolescent↗
PubMed1989

In vitro fixation of C3d and C5b-9 on platelets by human platelet reactive antibodies.

Most platelet-reactive autoantibodies and alloantibodies are not able to fix complement in vitro. However, exceptions have been found. These antibodies are usually characterized by the conventional platelet complement fixation test. A recently developed competitive enzyme immunoassay for quantitation of platelet-associated immunoglobulins and a modification thereof allowed the quantitative study of fixation of C3d and the membrane attack complex (C5b-9) on platelets by HLA antibodies, human platelet autoantibodies, and drug-dependent antibodies (ddab). The highest amounts of both complement products were fixed through ddabs, whereas autoantibodies only showed moderate complement fixation. This enzyme immunoassay is a valuable tool for the characterization of the complement-fixing properties of platelet-reactive antibodies.

Antibodies↗
PubMed1989

Recent trends in platelet antigen/antibody detection.

The detection of platelet antigens and platelet antibodies has always been difficult. Recent technical achievements are due to the availability of more specific and sensitive reagents (i.e. F(ab)2 fragments; higher specific activity of labels; monoclonal antibodies directed against platelet membrane constituents etc.) and the application of advanced immunological assays to platelet immunology (i.e. blotting assays, "capture"-ELISA's and radioimmunoprecipitation in conjunction with SDS polyacrylamide gel electrophoresis). These techniques have permitted the definition and immuno-chemical characterization of new platelet allo- and autoantigens, have assisted in clinical diagnosis and promoted our understanding of pathogenic mechanisms. Illustrative examples are presented and discussed.

Antibodies↗
PubMed1989

High-dose IgG treatment for neonatal alloimmune thrombocytopenia.

Twelve children with neonatal alloimmune thrombocytopenia (NAT) due to Zwa incompatibility were treated with intravenous IgG (IVIG). Total doses ranged between 1 and 9 g. Ten out of 12 infants had a favorable response. It is concluded that IVIG can serve as an emergency treatment in NAT if material (or compatible) platelets are not available.

Blood Platelets↗
PubMed1989

Identification of the target platelet glycoprotein in autoimmune thrombocytopenia occurring after allogeneic bone marrow transplantation.

We report the case of a patient who developed autoimmune thrombocytopenia after allogeneic bone marrow transplantation from her HLA-identical sister. An IgG autoantibody was detected that bound to the platelet glycoprotein IIb/IIIa and to the HLA class I proteins. Immunoprecipitation studies with radiolabeled platelets revealed additional antibody binding sites on proteins of 214 kDa molecular weight under nonreduced conditions and 65 and 56 kDa molecular weight under reduced conditions.

Adult↗