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G Mueller-Eckhardt

Publications and source records attributed to G Mueller-Eckhardt.

At least 37 records · Page 2Linked to original sources

[Granulocyte-specific and HLA antibodies in pregnancy: incidence and clinical value].

Postpartum sera of 1,016 unselected women were examined for granulocyte-specific and HLA antibodies. A total of 11 out of 1,016 sera (1.1%) were only reactive with neutrophils. Cytotoxic HLA antibodies were detected in 24%, noncytotoxic HLA antibodies in 4.8% of the sera. All antibodies belonged to the IgG 1 and IgG 3 subclasses. NA1 and NB1 specificity were each determined in one serum, two sera contained NA2-specific antibodies. After 1 year all antibodies were no more detectable. As none of the newborns from immunized mothers developed neutropenia, the incidence of alloimmune neonatal neutropenia seems to be lower than 0.1%.

Autoimmune Diseases↗

Autoimmunization against the neutrophil-specific NA1 antigen is associated with HLA-DR2.

A significant association of autoimmune neutropenia (AIN) in infants due to NA1-specific autoantibodies and HLA-DR2 is reported. Nineteen of 26 infants presenting with AIN and NA1 autoantibodies possessed the DR2 antigen, while only one out of six children with AIN, but non-NA1-specific autoantibodies, was DR2 positive. Furthermore, one adult patient with primary biliary cirrhosis and periods of neutropenia due to NA1 autoantibodies also carried the DR2 antigen. All DR2-negative patients were positive for DRw6. These findings indicate that a close relationship exists between autoimmunization against the NA1 antigen and HLA-DR2 and possibly also DRw6.

Aged↗

HLA association of idiopathic Peyronie's disease: an indication of autoimmune phenomena in etiopathogenesis?

HLA typing for class I and class II antigens was done in 52 unrelated patients suffering from idiopathic Peyronie's disease. The controversially discussed association with the HLA-B7 cross-reacting group could not be confirmed. Marked deviations of antigen frequencies were observed for HLA-A1, B8, Cw7, DR3 and DQw2 compared to healthy local controls. After correction of p-values, A1 (pc less than 0.05) and DQw2 (pc less than 0.01) remained significant. A possible association of Peyronie's disease with markers of the HLA-A1, B8, Cw7, DR3, DQw2 haplotype, as first described here, would suggest autoimmunological factors in this disorder of otherwise unknown etiopathogenesis.

Adult↗

HLA typing and lymphocytotoxic crossmatches using conventional techniques or immunobeads. A comparative study.

In a prospectively designed comparative study, HLA class I and class II typing was performed after B/T lymphocyte separation by nylon wool (NIH technique) or using immunomagnetic beads (IMB technique). Samples from 70 healthy individuals (group A) and from 47 patients with potential typing problems (group B) were examined. Complete typing failures occurred more frequently with NIH than with IMB. Except for class I in group A, the rate of correct decisions for antigen assignment was significantly higher with IMB. For class II serum reactions, specificity, predictive value and efficiency were superior for IMB, while sensitivity appeared higher for NIH. This can possibly be explained by a prozone effect which was observed in 9 of 36 titration experiments only with the IMB technique. Correlation of both methods in 104 crossmatches prior to kidney transplantation was poor using peripheral blood lymphocytes, but excellent with spleen cells. In addition to the important advantages of the IMB technique for potential problem cases, especially for class II, typing time is reduced to one third, which is of particular clinical importance in kidney transplantation. However, lymphocytotoxic crossmatches prior to transplantation, if performed by IMB, should be carried out using different serum dilutions or with donor spleen cells instead of peripheral blood lymphocytes.

Antibodies, Monoclonal↗

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↗

[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↗

[Passive immunotherapy with polyvalent immunoglobulins in women with habitual abortions].

Intravenous immunoglobulins (IVIG) were used in an alternative approach to immunotherapy with allogeneic leukocytes to prevent recurrent spontaneous abortions (RSA). Twenty five women with a history of greater than or equal to 3 unexplained RSA were treated with IVIG during their next pregnancy. An initial dose of 30 g (0.5-0.6 g/kg body weight) was administered at gestational week 5-6. Treatment was continued every 3 weeks with 20 g (0.3-0.4 g/kg) and terminated by week 25. In primary RSA the success rate was 82-85%, which is in the same range as for leukocyte therapy. In contrast, IVIG was successful in only 40% of secondary aborters. We conclude that IVIG can be an effective treatment for prevention of primary RSA. Compared to leukocyte therapy the risks of transmission of infections and of HLA immunization can be avoided.

Abortion, Habitual↗

[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↗

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↗

Pregnancy-maintaining antibodies: workshop report (Giessen, 1988).

To analyse the nature of antibodies which are purported to be essential for the maintenance of normal human pregnancy, six centers participated in a workshop of "blind" tests on 19 allosera. Fc-receptor dependent assays detected antibodies with specificity only for HLA. In addition to cytotoxic antibodies, the Fc-receptor dependent immune phagocytosis inhibition test revealed two non-cytotoxic alloantibodies with HLA specificity. These antibodies had high titers and may, therefore, be essentially non-cytotoxic. Murine monoclonal antibodies to HLA-A, B, C or DR (W6/32 and 2MC3) were used to evaluate the methods. These antibodies inhibited immune rosette formation as well as immune phagocytosis. Diluted to concentrations below the threshold of complement-dependent cytotoxicity, the monoclonal antibodies still inhibited the mixed lymphocyte reaction and the immune phagocytosis. A human monoclonal immunoglobulin M with specificity for monomorphic non-HLA lymphocyte antigens inhibited the mixed lymphocyte reaction. The immune rosette inhibition test exhibited several false positive reactions, e.g. three out of four with a serum that did not contain alloantibodies to blood cells. Non-cytotoxic antibodies were therefore rare in the selected sera of the workshop and they exhibited HLA specificity only. No participant was able to identify pregnancy-maintaining non-HLA-antibodies.

Abortion, Habitual↗

Influence of immunization with allogeneic spleen cells on the number of viable neonates in mice.

Female CBA/J (H-2k) mice mated with male DBA/2J (H-2d) mice show a high level of fetal resorption, which can be reduced by immunization with BALB/c (H-2d) spleen cells. The morphologically defined fetal resorption rate upon which evaluation of the outcome of pregnancy has previously been based in this strain combination is not equivalent to the rate of production of viable neonates.

Abortion, Habitual↗

Discrimination of antibodies against antigens of different MHC loci in human sera by monoclonal antibody-specific immobilization of leukocyte antigens.

To detect human antibodies against antigens of different major histocompatibility complex loci, particularly of class II specificity, a newly developed enzyme immunoassay for platelet antibodies was adapted for the use of lymphocytes as target cells. Peripheral blood lymphocytes, phytohemagglutinin-stimulated T cells, or Epstein-Barr virus-transformed B cells were simultaneously incubated with a monomorphic class- or locus-specific monoclonal antibody and the human antibody to be investigated. After solubilization, cell lysates were transferred to an enzyme-linked immunosorbent assay tray coated with a goat anti-mouse Ig antibody. Following immobilization of the monoclonal antibody/antigen complexes, human major histocompatibility complex antibodies were detected by addition of enzyme-labeled goat anti-human Ig. By means of this technique human antibodies against different major histocompatibility complex molecules present in the same sample could be clearly distinguished. Application of the monoclonal antibody-specific immobilization of lymphocyte antigens assay is presented by several examples. Of these, identification of DP-specific antibodies as well as serological DP typing are of particular interest.

Antibodies, Monoclonal↗

[Diagnosis in patients with habitual abortion].

Since promising immunological concepts for treatment of patients with three or more miscarriages have been introduced, an exact clarification of all possible etiological factors has become even more urgent, because an infection risk associated with leucocyte therapy cannot be ruled out. Own experiences with 47 couples with a history of habitual abortion who had been diagnostically evaluated in a special screening program in our hospital between 1985-1988 are discussed in the light of surveys of the recent literature. A critical revision of several factors which had been classified as etiological factors of habitual abortion in the past, seems important. While genetic factors are undoubtedly the most important cause of miscarriages in the first trimenon, the role of anatomical uterine anomalies (amongst our patients in 7 per cent), luteal insufficiency (among our patients in 9 per cent) and endometriosis cannot be evaluated with certainty yet because different diagnostic criteria have been established for diagnosis in the literature. Based on newly published data immunological factors seem to become etiologically more important; other anomalies, like infections or diabetes do not seem to be associated with an increased risk for habitual abortion. According to our experiences, habitual abortion may present as a problem involving different pathogenetic factors (among our patients in 79 per cent) so that sequential therapeutic steps may be required for treatment of a-possibly-multifactorial disease.

Abortion, Habitual↗

HLA-DP antigens in patients with chronic autoimmune thrombocytopenia (AITP).

AITP, a disease with well-defined autoimmune character, has been previously studied for a possible HLA association. However, no such association with antigens of the A, B, C or DR loci was found. As this does not exclude a possible association with HLA-DP antigens, we have investigated 36 patients with AITP for DP w1, w2, w3, w4 and w5 by primed lymphocyte typing using locally derived as well as the original DP reagents as used in the 9th International Histocompatibility Workshop. Comparison of antigen frequencies with those of 254 healthy controls revealed an increased frequency of DPw5 in the patient group which, however, was not statistically significant. Other discrepancies were not observed.

Adolescent↗

Prevention of recurrent spontaneous abortion by intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) treatment was attempted as a novel therapeutic approach for unexplained recurrent spontaneous abortions (RSA) occurring in the first trimester of pregnancy. Twenty women with a history of RSA were treated with IVIG during pregnancy. Therapy was commenced at week 5 of gestation with 1 dose of 0.5-0.6 g IVIG/kg body weight. Infusions were repeated every 3 weeks (0.3-0.4 g/kg) and terminated by week 22 to 24. Of 20 women, 11 delivered healthy infants at term. 5 women are still pregnant, 3 in the third trimester. Only 3 patients suffered abortions and 1 presented with ectopic pregnancy. The overall success rate was 82-86%. Thus, the therapeutic effect of IVIG is comparable to that of the conventional transfusion/vaccination regimen with allogeneic leukocytes, but avoids the risk of transmission of infections and/or HLA immunization, has no major adverse effects and is applicable to 'nonresponders'.

Abortion, Habitual↗