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C Mueller-Eckhardt

Publications and source records attributed to C Mueller-Eckhardt.

At least 199 records · Page 11Linked to original sources
PubMed1986

Neonatal alloimmune thrombocytopenia due to fetomaternal Zwb incompatibility.

A case of neonatal alloimmune thrombocytopenia due to fetomaternal incompatibility against the platelet-specific antigen Zwb (PlA2) is described. The antibody was of the IgG class and did not fix complement in vitro. Its specificity was established by panel identification and by comparison to a Zwb antiserum. Gene dosage determinations of Zwa antigens on platelets of parents and child revealed that the mother was homozygous Zwa Zwa, while father and child were heterozygous for this antigen.

Adult↗
PubMed1986

Binding of murine monoclonal antibodies to human MHC class I or II antigens increases binding sites for either antibody.

Membrane redistribution of major histocompatibility complex (MHC) class I and II antigens on human B lymphocytes and monocytes was studied quantitatively by fluorescence flow cytometry using monoclonal antibodies (mAb) w6.32 (class I-specific) and 2MC3 (class II-specific). It was shown that the surface density of class I and II antigens to which corresponding mAb had been bound decreased rapidly upon incubation at 37 degrees C. However, the total amount of class I antigens remained practically unchanged, while that of class II antigens increased substantially. This augmentation of class II antigens could be elicited not only by the corresponding class II-specific mAb but, similarly, also by non-corresponding class I-specific mAb. New expression of class I antigens only compensated for removed antigens. The speed of disappearance was comparable for antigens of either class. We conclude that the more pronounced expression of new class II antigens is not due to a greater surface mobility, but to a faster recycling and/or larger intracellular deposits of the antigens. This uneven redistribution of class I and II antigens is likely to reflect differences of function known to be dependent on MHC products.

Animals↗
PubMed1986

Receptor patching and capping of platelet membranes induced by monoclonal antibodies.

Redistribution of glycoproteins (GP) Ib, glycocalicin, IIb, and IIIa on the surface of human platelets in response to stimulation with corresponding monoclonal antibodies (MoAb) and a polyclonal antiglycocalicin antibody was studied by immunofluorescence, immunoelectron microscopy, and a quantitative radioimmune assay. Immobilization of the antigens by prefixation with formaldehyde showed a uniform distribution over the surface of the platelet. Incubation of unfixed platelets with specific MoAb against various epitopes on GPIIb and/or IIIa resulted in a time-dependent patching, subsequent capping, and after prolonged exposure to the antibody/label complex, internalization of the complex, possibly by endocytosis. In contrast, GPIb could not be shown to cap. From these results we conclude that platelet GPIIb and/or IIIa undergo spatial rearrangement in a manner analogous to that observed in lymphocytes, whereas GPIb does not. Since both GPIb and GPIIb and/or IIIa seem to be transmembraneous GP associated with the cytoskeleton, a special, though unidentified, role of GPIIb/IIIa in the induction of lateral membrane mobility is postulated.

Antibodies, Monoclonal↗
PubMed1986

Acquired thrombasthenia due to GPIIb/IIIa-specific platelet autoantibodies.

An otherwise healthy woman developed a hemorrhagic diathesis with fluctuating clinical symptoms and laboratory findings, but without thrombocytopenia, over 8 years. In periods of bad clinical condition, a platelet defect, characteristic of thrombasthenia, was found. In contrast to classic thrombasthenia, electrophoresis of the patient's platelet membranes revealed normal amounts of glycoproteins IIb alpha, IIb beta, and IIIa in the normal positions. Monoclonal antibodies, specific for GPIIIa and GPIIb/IIIa, respectively, bound normally to the P1A1-positive platelets from the patient. Although no antibody and no platelet function inhibitor were evident in the autologous plasma, an IgG1 antibody that was bound to the patient's platelets and was directed against GPIIb/IIIa could be demonstrated. After elution from the patient's platelets, this antibody immunoprecipitated GPIIb (both subunits), IIIa, and a 200-kilodalton (kd) band (probably undissociated GPIIb/IIIa complex) from solubilized normal platelets, but did not react with thrombasthenic platelets. Adding the eluate from the patient's platelets to normal platelet-rich plasma immediately caused concentration-dependent inhibition of adenosine diphosphate (ADP)-induced and collagen-induced aggregation and also strong inhibition of ADP-stimulated fibrinogen binding. Because it was very unlikely from the patient's medical history that the antibody was caused by alloimmunization, the hemorrhagic diathesis must be interpreted as acquired thrombasthenia due to an anti-GPIIb/IIIa autoantibody.

Adult↗
PubMed1986

Rh blood group-specific antibodies in immune hemolytic anemia induced by nomifensine.

Nomifensine (Merital, Alival; Hoechst, Frankfurt, FRG), an antidepressant drug, may cause immune hemolytic anemia (IHA) of the so-called immune complex type that is believed to occur by means of an innocent-bystander mechanism. In this report we describe findings that are not consistent with this mechanism in a patient with nomifensine-induced intravascular IHA associated with renal failure. In vitro studies showed a transitory positive direct antiglobulin test (DAT) due to IgG, IgM, and C3 fixation. The causative antibodies were found to be a drug-independent IgM antibody in the serum and eluate that reacted only with E-positive RBC, although the patient's RBC were E-negative; an IgG antibody in the serum and initial eluates that showed a stronger reaction with e-positive than with e-negative or Rhnull RBC, but only in the presence of ex vivo antigen (ie, urine containing the drug and all its metabolites); and an IgM antibody in the serum and initially also on the patient's RBC that, in the presence of ex vivo antigen as well as in the presence of known metabolites of the drug, agglutinated all RBC equally strongly, but was hemolytically more active against E-positive than E-negative cells. Within a few days of stopping the drug the hemolysis rapidly resolved without administration of prednisone, the DAT became negative with anti-IgG and anti-IgM, and the drug-independent anti-E disappeared, but both metabolite-dependent antibodies remained detectable in the patient's serum. We conclude that the production and specificity of the causative antibodies in this case were controlled by a larger antigenic site, presumably consisting of the drug and/or its metabolites plus RBC antigens, rather than by epitopes of the drug or metabolites alone.

Anemia, Hemolytic, Autoimmune↗
PubMed1985

Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood.

In a randomised, multicentre study intravenous IgG was compared with oral corticosteroids in 108 children with untreated acute immune thrombocytopenic purpura. IgG was an efficient treatment with no severe untoward reactions. The effects of corticosteroids and IgG were identical for rapid responders, who accounted for 62% of all patients. In contrast, patients requiring more than initial treatment responded better if randomised to IgG. The serum IgG level increased two-fold after IgG. A significant rise in IgM levels was observed after both IgG and corticosteroids. The platelet-associated IgG index was high in 75% of all patients. No significant differences between the two treatment groups were found, but rapid responders had a smaller mean initial platelet-associated IgG index which returned more rapidly and more permanently to normal than that of slow responders.

Acute Disease↗
PubMed1985

The role of metabolite-specific antibodies in nomifensine-dependent immune hemolytic anemia.

Nomifensine is an antidepressant drug (widely used in Europe, but not yet available in the United States), which has been linked to intravascular hemolysis. We studied 19 patients (18 women and 1 man) with acute intravascular hemolysis due to nomifensine-dependent antibodies. Transitory renal insufficiency developed in at least seven patients, and four required temporary dialysis. To investigate the antibodies, we used nomifensine, its three main metabolites, and its ex vivo antigens (urine samples from a volunteer collected 1.5 to 16 hours after the ingestion of 100 mg of nomifensine). We found an extraordinary heterogeneity of antibody response. Only five antibodies appeared to be primarily reactive with nomifensine. The remaining antibodies reacted either optimally or exclusively in the presence of one or more of the metabolites. Three of the metabolite-specific antibodies were positive only in the presence of ex vivo antigens, indicating specificity for as-yet-unidentified early and late metabolites of nomifensine. All the antibodies were capable of activating complement and belonged to the IgG or IgM class or both. Two serum samples also contained weak IgA antibodies. In addition to a variable degree of cross-reactivity of the antibodies, at least one serum sample had two drug-dependent red-cell antibodies (IgG against nomifensine and IgM against metabolites), and one sample had a drug-dependent IgM red-cell antibody and an IgG platelet antibody. Despite their serologic heterogeneity, all the antibodies were strongly reactive with ex vivo antigens. We recommend the use of ex vivo antigens as the technique of choice for the detection of nomifensine-dependent (and probably other drug-dependent) antibodies.

Acute Disease↗
PubMed1985

Monoclonal antibodies against human platelet membrane glycoproteins IIb-IIIa. II. Different effects on platelet function.

Preincubation of human platelets with two pairs of immunologically identical monoclonal antibodies (mab) directed against epitopes on the membrane glycoprotein IIb-IIIa complex - two of them (Gi3 and Gi5) precipitating glycoproteins IIb-IIIa, and two (Gi4 and Gi6) recognizing glycoprotein IIIa - induced slightly different inhibitory effects on platelet function. Gi3 and Gi5 blocked platelet aggregation and 14C-serotonin release from platelets induced by ADP, collagen, thrombin, arachidonic acid, ionophore A 23187, platelet activating factor and ristocetin (in the presence of divalent ions). Ristocetin-induced platelet agglutination (in the presence of EDTA) was not inhibited by these mab. Gi4 had no effect on platelet aggregation and release. Gi6 had the same effect on platelet function as Gi3 and Gi5, but only when incubated with Zw(a) (PlAl)-positive platelets with the exception that collagen-induced aggregation was not affected. We conclude that the similar, though not identical, effects on platelet function induced by mab against different epitopes on the glycoprotein complex IIb-IIIa indicate an "unspecific" interference with platelet membrane function possibly due to steric hindrance by mab of the fibrinogen receptor or by inhibition of conformational changes in the GP IIb-IIIa complex necessary for exposure of the fibrinogen binding site.

Antibodies, Monoclonal↗
PubMed1985

Platelet survival determined with 51Cr versus 111In.

Optimal labelling conditions of human platelets with 111In-oxine were determined in vitro. Based on this optimized technique, platelet mean life span (MLS) and platelet sequestration site were comparatively evaluated in 79 patients with two labels, 51Cr (n = 26) and 111In (n = 53). Patients were subgrouped according to clinical criteria as autoimmune thrombocytopenic purpura (AITP) (group 1; n = 49), hypersplenism (2; n = 12), impaired thrombopoiesis (3; n = 3), unclassified thrombocytopenia (4; n = 6), and nonthrombocytopenic patients (5; n = 9). In patients with AITP and hypersplenism the mean values for the MLS determined either with 51Cr or with 111In were lowered but the difference was not statistically significant, neither for group 1 (18.6 h vs 17.3 h; P greater than 0.2) nor for group 2 (94.7 vs 122.3 h; P greater than 0.2). The correlation between MLS and platelet counts in patients with AITP was significant for both labels (P less than 0.001). The 15 min recovery tended to be higher with 111In in all groups, but the difference was significant (P less than 0.05) only for group 1. The sequestration sites were similar with both labels. We conclude that, contrary to previous reports, platelet survival studies yield similar results with both the 51Cr and 111In methods. Due to its distinct advantages 111In is the label of choice for investigation of platelet kinetics.

Blood Platelets↗
PubMed1985

Murine monoclonal antibodies and human alloantisera specific for HLA inhibit monocyte phagocytosis of anti-D-sensitized human red blood cells.

Evidence is presented that monoclonal antibodies (mAb) against some human major histocompatibility complex (MHC) gene products and human sera containing HLA antibodies strongly inhibit immune phagocytosis of anti-D-sensitized red blood cells by human monocytes. w6.32HL, a mAb against a monomorphic class I antigen of high cell surface density, revealed the strongest inhibition among mAb reactive with MHC class I products. mAb with preferential reactivity for monomorphic and polymorphic DR and DQ epitopes (L203, L227, IIIE3, Tü22, Genox 3.53 and IV12) were noninhibitory. Definite inhibition was also apparent with a mAb against DRw52/MT2 (I-LR2) and with an antibody to class II antigens of high cell surface density (2MC3). Human sera containing HLA antibodies showed strong inhibition of immune phagocytosis up to a dilution of 1/1000. This inhibition could not be abrogated by platelet absorption. This indicates that human sera inhibiting immune phagocytosis may comprise at least two types of antibodies: cytotoxic HLA-specific antibodies which may or may not be inhibitory, and inhibitory antibodies against monocytic antigens not necessarily cytotoxic. These latter antibodies may recognize HLA DR or another as yet undefined gene product within, or closely associated to, the human MHC.

Antibodies, Monoclonal↗
PubMed1985

Chronic thrombocytopenia in an immunodeficient patient with hemophilia A.

Coincident hemophilia and idiopathic thrombocytopenia has been rarely observed. We report here on a young man with severe hemophilia A who was treated with concentrates of lyophilized antihemophilic factor for several years before he developed thrombocytopenia. An isolated thrombocytopenia coincident with reduced platelet survival, ample megakaryocytes in the bone marrow, elevated platelet-associated IgG, as well as remission after treatment with prednisone and splenectomy, suggest the idiopathic form of thrombocytopenia. In addition, defects in cellular immunity became obvious. A causal relationship between the application of blood-derived products and the development of the platelet disorder as well as the impairment of the T-cell system remain to be demonstrated.

Adult↗
PubMed1985

Gray platelet syndrome: selective alpha-granule deficiency and thrombocytopenia due to increased platelet turnover.

Clinical and laboratory studies of two siblings, both suffering from gray platelet syndrome (GPS) are described. The patients had a mild bleeding disorder, their platelets were blue-gray in panoptic stains, and alpha-granules were markedly reduced, as shown by electron microscopy. The platelet content of platelet factor 4 and that of beta-thromboglobulin were significantly reduced (3%-7% of normal). Platelet count was decreased (33-150 X 10(9)/1) and small platelets were increased in platelet volume distribution. Bleeding time was prolonged on most occasions. Bone marrow aspiration was performed in one patient and revealed increased reticulin fibers, however, megakaryocyte count was normal. The mean platelet survival was 4.8 days using 111indium-labelled platelets. In this patient, platelet-associated IgG was within the normal range. Prednisone therapy failed to increase platelet count. Dental surgery was performed under cover of desmopressin and no bleeding complication occurred; however, no improvement of bleeding time was observed. The patient delivered a healthy male infant without hemorrhaging while under concurrent platelet transfusion therapy.

Adult↗
PubMed1985

High-dose intravenous immunoglobulin for post-transfusion purpura.

Five patients with post-transfusion purpura (four due to Zw(a), one presumably due to HLA antibodies) were treated with intravenous immunoglobulin (IgG) at doses of 0.4 g per kg body weight. IgG therapy was immediately effective as indicated by cessation of bleeding and rise of platelet counts in four out of five cases.

Adult↗
PubMed1985

Interdependent membrane mobility of human MHC coded antigens detected by monoclonal antibodies to various epitopes on class I and II molecules.

Binding of monoclonal antibodies (MAB) to human MHC coded class I antigens, w6.32HL or 61D2, specifically leads to clustering of these antigens and their assembly at one polar site on a cell, whereby these class I antigens tow class II-antigens with them into the polar cap revealing preexisting or arising molecular complexes in the membrane of the living cell. These class II antigens included DR (seen by MAB 2MC3, L203, L227, I-LR2, 109d6, SFR-3) and DQ (seen by Genox 3.53 and IVD12). In analogous cocapping experiments employing MAB to various class II antigens, interdependent surface mobility (bidirectional cocapping) could be demonstrated between DRw52 (MT2, seen by I-LR2) and DQw3 (MB3, seen by IVD12) as well as between DRw53 (MT3, seen by 109d6) and DQw3. There was incomplete interdependence between DRw52 or DRw53, respectively, and other DR antigens (seen by L227). These latter antigens were independent from DQ (seen by Genox 3.53 or IVD12). Analyzing pairs of monoclonal antibodies with various specificities to determinants on class I or II molecules a frequent finding was unidirectional cocapping: here a first antibody cocapped epitopes seen by a second, but this antibody did not cocap epitopes seen by the first. We conclude that epitopes are irregularly distributed on MHC coded molecules or on complexes of these molecules.

Antibodies, Monoclonal↗
PubMed1985

Immunogenicity of and immune response to the human platelet antigen Zwa is strongly associated with HLA-B8 and DR3.

In a prospective study the immunogenicity of the Zwa antigen during gestation was investigated. Twenty-six out of 1,211 pregnant women were Zwa negative (2.15%). In 2 out of 23 Zwa negative mothers who delivered Zwa positive children, an antibody to Zwa was detected. To determine the relationship between the immune response of pregnant women towards Zwa and the MHC, the phenotype frequencies of HLA-A, B, C, DR, and complement BF, C2, C4A, C4B allotypes of "non-responders" without detectable Zwa antibodies (N = 20) were compared with a group of "responders", i.e. Zwa negative mothers giving birth to Zwa positive children with typical neonatal alloimmune thrombocytopenia (NAIT; N = 39) and with a normal control population. When compared to the normal control group, "non-responders" showed a significant increase of the DRw6 frequency, whereas in the "responders" group HLA-A1, B8, DR3, and C4A*QO were significantly elevated. If "non-responders" and "responders" were directly compared, only B8 and DR3 remained significantly different. The strongest association with a hypothetical immune response gene appeared to exist with DR3.

Antigens, Human Platelet↗
PubMed1985

A two-stage immunoradiometric assay with 125I-staphylococcal protein A for the detection of antibodies and complement on human blood cells.

A sensitive two-stage immunoradiometric assay (IRMA) using unlabeled specific antiglobulin sera followed by binding of radiolabeled staphylococcal protein A has been developed for detection of human IgG, IgM, IgA and complement C3 on human blood cells. In an experimental model system, purified human immunoglobulins (Ig) were coupled onto red blood cells, platelets, and leukocytes. The Ig-coated red blood cells were analyzed in parallel by three methods: the radioimmune antiglobulin test with radiolabeled anti-Ig; the radiolabeled staphyloccal protein A test, and the IRMA. Of the three methods evaluated, the latter was found to be sensitive and the easiest to perform. The applicability of the IRMA was established by investigating a group of 14 selected patients with autoimmune warm type hemolytic anemia. We observed that the IRMA detected cell-bound antibodies (IgG and/or IgM) in several cases where conventional assays yielded negative results.

Antibodies↗
PubMed1985

Endothelial monocyte antigens are coded for by loci centromeric of HLA-B.

900 pregnancy sera were screened for monocyte antibodies. 23 sera (2.6%) were found to be reactive with monocytes in an allotypic pattern distinct from blood group ABO, HLA-A,B,C, DR and DQ specificities. Because of strong reactions and high reproducibility, 4 sera with pure endothelial monocyte (EM) reactivity and 2 sera also positive with B lymphocytes of certain donors were selected for population and family studies. The frequency of positive reactions in a panel of 26 random donors obtained with the pure EM sera was 13, 8, 8 and 13% with clearly distinct patterns. Analysis of the tentatively designated EM antigens 1.1, 1.2, 2.1, and 2.2 in 7 families revealed definite segregation with HLA. By means of two crossing-over events within the HLA region the two hypothetical EM loci were localized centromeric of HLA-A and one of both loci centromeric of HLA-B.

Antigens, Surface↗