HLA-DRw6, a new immune response marker for immunization against the platelet alloantigen Bra.
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Adult↗
Biomedical subjects
G Mueller-Eckhardt
Publications and source records attributed to G Mueller-Eckhardt.
Cellular approach for detecting narcolepsy-specific alterations in DR2 haplotypes.
In an attempt to detect disease-associated genetic variations and/or exogenously induced alterations in DR2 haplotypes of narcolepsy patients, primed lymphocytes (PLs) were generated in nine families against DR2 haplotypes of narcolepsy patients and healthy family members. Twenty-four PL reagents were obtained and restimulated by cells of unrelated narcolepsy patients and DR2/Dw2-positive healthy individuals. The mean restimulation rates triggered by cells of patients or healthy controls, respectively, never differed significantly. In primary MLC as well as PLT combinations of patients and their HLA-identical siblings no significant stimulation was observed in both directions. We conclude that narcolepsy-specific alterations of class II molecules cannot be cellularly detected or do not exist on peripheral lymphocytes.
Female↗
Major histocompatibility complex markers in patients with nomifensine-induced immune hemolytic anemia.
To evaluate a possible role of major-histocompatibility-complex (MHC)-related immune-response genes for the selective production of drug-induced antibodies, HLA class I (ABC), class II (DR, DQ), class III (BF, C2, C4A, C4B) as well as glyoxalase-1 allotypes were investigated in 26 patients with nomifensine-induced immune hemolytic anemia. No statistically significant deviations of MHC antigen frequencies were noted. The possible implications of these findings are discussed.
Adult↗
Reduced immune phagocytosis of monocytes from neonates whose mothers produce HLA antibodies.
In vivo immune phagocytosis of neonatal monocytes was significantly correlated to the extent of maternal HLA immunization. Monocytes from all 15 neonates of mothers with HLA antibodies show reduced immune phagocytosis. In contrast, this holds true for monocytes from only 6 out of 13 neonates of mothers without detectable HLA antibodies. We infer the hypothesis that maternal HLA antibodies bind to mononuclear phagocytes of the fetus and of the fetal part of the placenta and thus cause inhibition of immune phagocytosis. Thereby, activation and secondary cell or tissue injury will not ensue and rejection of the fetal allograft is prevented in those pregnancies in which maternal alloimmunization occurs.
Female↗
Alloimmunization against the platelet specific Zwa antigen associated with HLA-DRw52 and/or DRw6?
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Antigens, Human Platelet↗
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↗
[Antibodies with B-lymphocyte specificity in pregnancy sera: the genetic and immunological characteristics].
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Antibodies↗
Posttransfusion purpura. A survey of 13 cases.
Thirteen cases of posttransfusion purpura (PTP) which were diagnosed in Germany and Austria from 1977-1985 are described. All patients were women with a mean age of 58.6 years (range, 36-77 years). All but one had been pregnant and received blood transfusions 2 to 12 days prior to the onset of PTP. The thrombocytopenic purpura was always severe with a nadir of platelet counts below 10 X 10(9)/l and lasted between 3 and 60 days. All patients recovered from PTP. Optimal therapy consisted of administration of high-dose IgG. Twelve of the 13 patients had developed platelet-specific Zwa antibodies (eight of them together with HLA antibodies), in one Zwa positive individual only HLA antibodies were detectable. Five of six HLA-DR typed patients carried DR3 which is considered an immunogenetic risk factor in PTP. Clinical awareness of this rare, but serious iatrogenic transfusion complication is prerequisite for prompt diagnosis and improved therapy.
Adult↗
Islet cell antibodies and the development of diabetes mellitus in relation to mumps infection and mumps vaccination.
Islet cell antibodies were investigated in 127 non-diabetic children after mumps infection and in four out of seven children who developed diabetes mellitus shortly after active mumps vaccination. Twenty-one of the children who had mumps and all four vaccinated children who were tested had islet cell cytoplasmic antibodies. In contrast, islet cell surface antibodies were detected in 43 out of 68 patients with mumps infection and in 32 out of 44 patients with other viral diseases. All but one mumps-infected child and all the other viral infected patients investigated did not develop diabetes mellitus. The mumps-infected ICA positive children did not show those HLA-frequencies associated with Type 1 diabetes.
Antibodies↗
HLA and narcolepsy in a German population.
In this paper the first MHC data including HLA-A, B, C, DR, DQ and complement BF, C4A, C4B determinants in German narcoleptics are presented together with the first family studies in European Caucasoids. 57 out of 58 unrelated patients (98.3%) were positive for DR2 and DQw1, respectively. In contrast to all other reports, one patient with typical signs of narcolepsy was found to be DR2/DQw1 negative. Data showing significant increase in the frequency of B7, and normal frequencies of B35 were discordant with data from Japanese patients. Definition of the extended DR2 linked haplotypes, deduced from 6 families, revealed that 5 out of 12 were DQw1, DR2, BFS, C4B1, C4A3, B7 (Cw7), while 11/12 had DR2, DQw1, BFS, C4A3, C4B1 in common. In one multiple case family two genotypically different DR2 haplotypes were identified in affected siblings. Results from the family study were concordant with a dominant mode of inheritance with incomplete penetrance of a hypothetical disease susceptibility gene.
Complement C4↗
HLA-B POT: a new HLA-antigen within the B7-cross reactive group.
In this report, a new HLA-B locus antigen is described (tentatively called POT). The antigen has been identified with antisera against the antigens that belong to the B7-cross reacting group. In a collaborative study, based on exchange of cells and sera, it was confirmed by population and family studies that the antigen is distinct from B7, Bw42 or Bw73 and is associated with Bw6. In absorption experiments with EBV-transformed cell lines, the POT-antigens removes preferentially anti-B7, Bw42 and Bw73 activity and to a lesser extent antibodies reactive with the B40 CREG-antigens.
Cross Reactions↗
HLA antigens on platelet membranes. In vitro and in vivo studies.
In order to determine whether HLA-A,B antigens of platelets are integral membrane constituents or rather represent adsorbed plasma proteins, their presence in plasma and their adsorbability onto platelet membranes was studied by in vitro and in vivo experiments. The amount of HLA antigens was quantitated by inhibition of lymphocytotoxicity (LCT) and by enzyme-linked immunosorbent assay (ELISA) using operationally monospecific polyclonal HLA antibodies or murine HLA-specific monoclonal antibodies, respectively. We found that in 11 out of 13 HLA-A2 and in 9 out of 10 HLA-B13 experiments, platelets from antigen-negative donors pretreated with plasma from the same number of antigen-positive donors inhibited LCT to the same extent as platelets from antigen-positive donors. Nevertheless, the in vitro adsorbed HLA antigens onto antigen-negative platelets were, unlike those on antigen-positive platelets or in plasma, not reactive with monoclonal antibodies as quantitated by ELISA. Similarly, infusion of HLA-A2-negative platelets from single donors into 3 HLA-A2-positive, thrombocytopenic patients with bone marrow failure led to a good platelet increment, but did not convert the HLA type of donor platelets, neither at 2 h nor at 18 h posttransfusion. On the basis of these results, we conclude that soluble HLA antigens can be taken up by human platelets from plasma in small amounts. However, the major portion of HLA antigens appears to be integral membrane constituents.
Adsorption↗
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↗
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↗
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↗
Possible association between HLA-DR5 and superficial spreading melanoma (SSM).
Previous analyses of possible associations between MHC determinants and cutaneous malignant melanoma (MM) have been inconclusive. We have investigated 98 patients with special emphasis on histologically determined subtypes of MM, and 5 multiple-case families. In addition to HLA-ABC and DR typing, complement allotypes of C2, C4A, C4B, BF were determined. Among the unrelated patients HLA-DR5 and, secondarily, B49 were observed to be associated with superficial spreading (SSM) but not with nodular (NM) or lentigo maligna melanoma (LMM). In families with MM, no definite segregation of the disease according to HLA and complement haplotypes was discernible. Moreover, no coincidence of haplotypes occurred in patients of the different families. HLA region recombinations including B/DR and/or DR/GLO were found in all the families investigated.
Adolescent↗
C4 allotyping distinguishes HLA-B14.1 and B14.2 subgroups.
Complement allotyping (C4, C2, and BF) was performed in 60 unrelated individuals and 15 families characterized for the subtypes (14.1 and 14.2) within HLA-B14. Eighty-seven percent of B14.2 individuals typed positive for the rare C4A2 variant. In contrast, less than 7% of B14.1 individuals were positive for this C4 allotype which is in keeping with a control background frequency. Family studies revealed that three distinct complotypes (complement haplotypes) are characteristic for the two HLA-B14 subgroups. The SC22 and FC31 complotypes characterize the B14.2 subtype, whereas SC31 appears to define B14.1.
Complement C4↗
Complications of mumps infection, islet-cell antibodies, and HLA.
To investigate whether the development of islet-cell antibodies (ICA) in the course of mumps infection is associated with a "diabetes-like" immunogenetic condition, 45 children with mumps complications as well as 56 children with insulin-dependent diabetes mellitus (IDDM) were typed for HLA ABC and DR antigens. ICA were detected in 14 out of 35 mumps patients. In the IDDM group, significant deviations from antigen frequencies of normal controls were observed for HLA Bw39, DR2, DR3, and DR4. In contrast, in ICA positive mumps patients, the frequency of these antigens was normal, but Aw24 was significantly increased. Thus, no immunogenetic similarities of both groups of patients could be detected.
Adolescent↗