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C Mueller-Eckhardt

Publications and source records attributed to C Mueller-Eckhardt.

At least 163 records · Page 9Linked to original sources
PubMed1988

A new platelet-specific alloantigen Bra. Report of 4 cases with neonatal alloimmune thrombocytopenia.

Sera obtained from 4 mothers of children with neonatal alloimmune thrombocytopenia contained a platelet-specific alloantibody, anti-Bra, which defined an antigen apparently different from all known platelet alloantigens. All 4 fathers were Bra positive, whereas all mothers were Bra negative. The minimal postnatal values of platelet counts ranged from 19 X 10(9) to 75 X 10(9)/1. Family studies showed that the Bra antigen is inherited as an autosomal, codominant trait. Its antigen frequency in the German population is 20% (21 of 105 unrelated donors were positive). The estimated gene frequency is 0.11. The antibodies were identified by a glycoprotein-specific enzyme immunoassay using monoclonal antibodies for antigen immobilization, while they could not reliably be detected by binding assays employing whole platelets (platelet immunofluorescence, indirect competitive ELISA).

Adult↗
PubMed1988

Complement-independent lysis of human red blood cells by cold hemagglutinins.

Hemolysis mediated by human antibodies is generally ascribed to the attack of red blood cells (RBC) by complement. We here extend earlier in vitro observations which indicate that potent cold agglutinins can directly cause lysis of RBC without the participation of complement. We have noted that EDTA plasma taken from patients with cold agglutinin disease is frequently reddish if the plasma is not immediately separated from the cells at 37 degrees C. Moreover, eluates prepared in such cases from plasma or heat-inactivated serum (30 min at 56 degrees C) by absorption (at 4-20 degrees C) and elution (at 37 degrees C) are usually contaminated with hemoglobin, and a large number of RBC used for absorption is lost during the procedure. To characterize this phenomenon further, we examined the effect of different hemagglutinating antibodies in vitro on normal RBC in the absence of complement. Hemolysis (5-17%) of RBC only occurred after treating the cells with potent antibodies at low temperatures (0-20 degrees C). This hemolysis increased 2- to 3-fold when the RBC were treated with an enzyme and decreased with rising temperature. Unlike cells hemolyzed by complement activation, no C5b-9 complexes could be detected on RBC damaged by this mechanism.

Cold Temperature↗
PubMed1987

Redistribution of platelet glycoproteins induced by allo- and autoantibodies.

The redistribution of platelet glycoproteins (GP) Ib, IIb and IIIa in response to stimulation with human platelet specific alloantibodies, autoantibodies and a quinidine-dependent antibody was investigated using immunofluorescence and a quantitative radioimmunoassay. The platelet GPs carrying the corresponding epitopes were determined using immunoblot technique or radioimmunoprecipitation. In accordance with previous results obtained with murine monoclonal platelet specific antibodies, redistribution upon stimulation with human platelet reactive antibodies was observed only due to reactions with epitopes on GP IIb, IIIa, respectively, but not on GP Ib. We therefore believe that membrane redistribution of human platelets induced by various antibodies is a function of the GP recognized by those antibodies rather than the source of the platelet reactive antibody.

Antibody Specificity↗
PubMed1987

Possible male segregation distortion of DR2 haplotypes in narcolepsy patients.

Segregation of disease-associated DR2-linked haplotypes from patients with narcolepsy was studied in 18 German families. Of these, 13 were informative, as transmission could be traced from DR2 heterozygous patients to their healthy offspring. Although the composition of extended haplotypes was equal in males and females, DR2 was transmitted to 78.6% of the offspring by diseased fathers but only to 57.1% by diseased mothers. Compared to an expected 1:1 ratio according to Mendelian segregation this means a statistically significant deviation (p less than or equal to 0.03) for male but not for female patients. In contrast, transmission distortion was not observed with 30 DR2 haplotypes in 27 healthy families. These data represent a new example of male segregation distortion in an HLA-associated disorder.

Female↗
PubMed1987

Cianidanol and its metabolites bind tightly to red cells and are responsible for the production of auto- and/or drug-dependent antibodies against these cells.

Cianidanol ((+)-2-(3,4-dihydroxyphenyl)-3, 5, 7-chromantriol) is a flavonoid which has been associated with severe immune haemolysis by as yet unclear mechanisms. We report six patients who developed haemolysis while receiving the drug. The disorder was episodic in all patients and resolved after discontinuing the drug. The causative antibodies could be demonstrated in all six cases, even when the haemolytic episode was more than 1 year prior to this study. One patient had developed drug-independent IgG autoantibodies, another simultaneously developed autoantibodies and drug-dependent antibodies (ddab) of the IgG class, while the remaining four patients had only ddab of the IgM and/or the IgG classes. All ddab were reactive with red blood cells (RBC) in the presence of the drug and/or its metabolites (ex vivo antigens), and, quite unexpectedly, also with RBC coated with the drug (metabolites) in vitro or in vivo. This reactivity did not change either by preincubating the antibodies with the drug or by adding large amounts of the drug to the mixture of drug-coated cells plus antibody. It seems that the stable association of cianidanol with RBC generates antigenic sites against which a heterogeneous immune response is elicited giving rise to long-lasting drug-dependent antibodies as well as autoantibodies.

Adult↗
PubMed1987

Haemolytic 'efficiency' of C5b-9 complexes in drug-induced immune haemolysis: role of cellular C5b-9 distribution.

We report on quantitative analyses of C5b-9 binding to target red blood cells (RBC) lysed through the action of drug (nomifensine)-dependent antibodies (ddab) and anti-RBC antibodies (warm plus cold agglutinins). Immunoradiometric assays showed that, at any given degree of haemolysis, more C5b-9 was bound to cells sensitized with anti-RBC antibodies compared to cells lysed via ddab. Thus, C5b-9 complexes deposited through the action of ddab appeared to be haemolytically more 'efficient' than those deposited via anti-RBC antibodies. However, data obtained from flow-cytometric assays and immunoelectron microscopy demonstrated a major role for the distribution (total number) of C5b-9 lesions among the cells within a given cell population. Enhanced haemolysis with a given total amount of C5b-9 complexes appeared to be derived from a more even distribution of these complexes among the cells rather than from higher lytic efficiency of individual complexes. Since ddab bind with low affinity to cells, we suggest that these antibodies diffuse from cell to cell and cause extensive haemolysis through the deposition of relatively few C5b-9 complexes at each site. In contrast, high affinity antibodies remain largely bound to relatively restricted sites causing deposition of larger amounts of C5b-9 on, and hence lysis of, numerically fewer cells. With respect to the net intravascular haemolytic effect, our findings may explain why complement-activating antibodies of low affinity are often more detrimental than high affinity antibodies.

Antibody Affinity↗
PubMed1987

Autoimmune haemolytic anaemia in childhood associated with non-complement binding IgM autoantibodies.

Red cell bound IgM autoantibodies free of associated IgG autoantibodies and unable to activate complement have not yet been considered as the cause of autoimmune haemolytic anaemia (AIHA). We report on warm type AIHA resulting from the action of IgM autoantibodies on circulating RBC. Twelve children (eight of whom were infants) with relatively severe haemolytic anaemia were studied. Whereas the clinical findings and courses of all children appeared to be compatible with warm type AIHA, the serological findings during the haemolytic phase were atypical in that the direct antiglobulin test (DAT) was negative in 11, and positive in one case due to C3d only. The use of radiolabelled antihuman globulin antibodies showed, however, that the RBC of all the patients were sensitized with warm IgM antibodies. Elevated values of IgA and/or IgG immunoglobulins on the patients' RBC were found to be present in only two cases. Complement activation by IgM autoantibodies could not be detected in all other cases neither in vivo nor in vitro. Thus, we conclude that non-complement binding IgM autoantibodies were responsible for the AIHA in the majority of these children possibly representing an as yet unrecognized variant of warm type AIHA.

Anemia, Hemolytic, Autoimmune↗
PubMed1987

Identification of the Yukb allo-antigen on platelet glycoprotein IIIa.

The glycoprotein (GP) localization of a new platelet-specific allo-antigen Yukb is described. The antibody was isolated from serum of a patient with neonatal allo-immune thrombocytopenia. In immunoblot procedure, it bound exclusively to platelet GP IIIa, like anti-PlA1, while the known anti-Baka and anti-Leka reacted with GP IIb. Analysis of GP from chymotrypsin-treated platelets with anti-Yukb revealed no binding in the 68-kilodalton position while anti-PlA1 did. Thus, unlike the PlA1 antigen, the Yukb determinant either resides on the 30-kilodalton fragment of GP IIIa or it is destroyed by chymotrypsin treatment.

Antibody Specificity↗
PubMed1987

Competitive enzyme-linked immunoassay for the quantitation of platelet-associated immunoglobulins (IgG, IgM, IgA) and complement (C3c, C3d) with polyclonal and monoclonal reagents.

A competitive enzyme-linked immunoassay (CELIA) was developed for the quantitation of platelet-associated immunoglobulins and complement proteins. The use of unlabeled polyclonal rabbit or monoclonal antibodies to human immunoglobulins and enzyme-labeled anti-mouse or anti--rabbit IgG (double-step technique) resulted in a higher sensitivity compared to the single-step technique using only enzyme-labeled anti-human immunoglobulin antibody preparations. Sensitivity and results obtained by both techniques were compared. The range of normal values for platelet-associated IgG, IgM, IgA, C3c and C3d was assessed upon a large number of normal blood donors. When platelet-associated IgG was concomitantly assayed with polyclonal and monoclonal anti-IgG by the double-step technique on platelets obtained from normal donors and thrombocytopenic patients, identical results were obtained with both reagents. Problems related to the quantitation of immunoglobulins on platelets with different assays and antibody preparations are discussed.

Antibodies, Monoclonal↗
PubMed1987

Pedigree of the major histocompatibility complex in a family with a neonatal alloimmune thrombocytopenia.

Immunization of a mother negative for the platelet-specific antigen P1A1 against the P1A1 antigen of her child induced neonatal alloimmune thrombocytopenia. This prompt immune response occurred in her first pregnancy and we were therefore interested to study whether there is an association with genes located within the major histocompatibility complex. We deduced haplotypes of HLA-A, B, C and DR as well as of complement C2, C4 and Bf in the maternal family members.

Adult↗
PubMed1987

On the mechanisms of sensitization and attachment of antibodies to RBC in drug-induced immune hemolytic anemia.

The mechanisms of sensitization and attachment of drug-dependent antibodies to RBC in drug-induced immune hemolytic anemias are largely speculative. Nomifensine has been incriminated in causing immune hemolysis in a large number of patients. The hemolysis was usually of the so-called immune complex type, less commonly of the autoimmune type, and more surprisingly, few patients had developed both types of hemolysis. To determine whether nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity for antigenic structures of RBC membranes, 30 ndab were tested against large panels of RBC with common and rare antigens. We found that only 14 out of 30 ndab were invariably reactive with all cells tested. Nine antibodies were, similar to the majority of idiopathic or drug-induced autoantibodies, not or only weakly reactive with Rhnull RBC. Three antibodies did not react with cord RBC and could be inhibited by soluble I antigen. The remaining four antibodies gave inhomogeneous reaction patterns or were even negative with selected RBC; their specificity could not be identified. On a Scatchard plot analysis of one ndab, a maximum of 173,000 drug-dependent antibodies of the IgG class can specifically bind per RBC in the presence of the drug. Although nomifensine and its metabolites do not attach tightly onto RBC, our results clearly indicate that RBC do not act as "innocent bystanders," but rather serve as a surface for a loose attachment of drugs that possibly cause a subtle structural change in the cell antigens and, by this means, allow in vivo sensitization; and a specific binding of the resultant antibodies. This concept would explain why these antibodies can be directed against drug-cell complexes, against cell antigens alone (autoantibodies), or against both in the same patient.

Anemia, Hemolytic, Autoimmune↗