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H Leibl

Publications and source records attributed to H Leibl.

16 recordsLinked to original sources
PubMed1992

IgG subclass determination in human sera with commercially available reagents: comparison of different assay systems.

IgG subclass determinations are of increasing importance for the diagnosis of humoral immunodeficiencies. The search for a method which is accurate, reliable and suitable for the clinical routine, while utilizing commercially available reagents, was the aim of this study. Different assay systems for determination of IgG subclasses were compared. Radial immunodiffusion with polyclonal antisera (RIDpoly) proved to be a reliable method for subclass determination in individual human sera. Sera deficient in one or several IgG subclasses as well as several myeloma proteins were readily and reliably detected. The RID method with monoclonal antibodies (RIDmono) yielded results comparable to those obtained with RIDpoly in the IgG1 and IgG2 determination. Differences between RIDpoly and RIDmono were observed, however, in the determination of IgG3 and IgG4. These discrepancies were shown to be due to differences in the calibration of the standards as given by the manufacturers, and not to different recognition of distinct allotypes. The results of an enzyme immunoassay (EIA) using commercially available IgG reagents without further purification did not compare satisfactorily with the results of the RIDpoly method. These discrepancies, however, were assay-inherent rather than monoclonal reagent-inherent.

Antibodies, Monoclonal↗
PubMed1991

Increased Fc-receptor-mediated clearance via reticuloendothelial system in patients with nephrotic syndrome.

Reticuloendothelial phagocytic cell function, which is an important participant in host defense, was investigated by studying the Fc-receptor-mediated clearance of IgG-anti-RhD-sensitized radiolabelled autologous erythrocytes in patients with nephrotic syndrome known to have an increased risk of infectious complications due to hypogammaglobulinemia. Patients with serum IgG concentrations less than 500 mg/dl had a significantly accelerated Fc-receptor-mediated clearance (t1/2 = 52 +/- 3.6 min) compared to patients with IgG levels greater than 500 mg/dl (t1/2 = 93 +/- 17 min) or healthy controls (t1/2 = 100 +/- 7.5 min). Serum IgG concentrations correlated significantly with Fc-receptor-mediated clearance (t1/2: r = 0.70; p = 0.035) in patients with nephrotic syndrome. These results indicate that Fc-receptor-mediated clearance by the reticuloendothelial system is enhanced in patients with nephrotic syndrome with low serum IgG concentrations and may, at least in part, compensate for reduced opsonic antibody concentration.

Adult↗
PubMed1991

IgG subclasses and antibody response to pneumococcal capsular polysaccharides in children with severe sinopulmonary infections and asthma.

A prospective open study was carried out on 30 pediatric patients with most severe chest disease whose serum immunoglobulin levels were normal. The patients entered into the study had had two or more documented episodes of pneumonia, and/or six episodes of bronchitis with fever within a year, and/or severe asthma (steroid-dependent), and/or hospitalization for chest disease for more than 30 days within the year preceding the study. Eleven patients had sinopulmonary infections, 19 had asthma. Twenty patients had low levels of one or two IgG subclasses: 11 were deficient in IgG3, three in IgG4, three in IgG3 + IgG4, and three in IgG2 + IgG4. Patients with low IgG subclass levels were distributed throughout the different clinical entities. These children had significantly longer periods of hospitalization than the patients in whom all IgG subclasses were within the normal range. They suffered more often from sinopulmonary infections. Asthmatic children with low levels of an IgG subclass reported more days with wheezing and needed more steroids than the children without subclass deficiencies.

Antigen-Antibody Reactions↗
PubMed1991

Determination of cyclosporine by a competitive binding assay with cyclophilin.

A competitive protein-binding assay for cyclosporine based on use of the intracellular cyclosporine-binding protein cyclophilin (CYP) was used to measure cyclosporin A (CsA) and its bioactive metabolites in whole blood. CYP from cytoplasmic extracts or erythrocyte lysates was applied in the binding assay with use of [3H]CsA as tracer and charcoal adsorption for separating bound from free tracer. Binding affinities of various CsA analogs and metabolites correlated well with their reported in vitro immunosuppressive activities. The assay detected as little CsA as 50 micrograms/L (1 g = 0.832 mmol of CsA), analytical recovery was greater than 80%, and CVs were less than 8% for intra-assay and less than 11% for interassay precision in the range of 150-1000 micrograms/L. We used this assay to measure CsA concentrations in blood and compared the results with those measured by HPLC or by CsA-specific (monoclonal) and CsA-nonspecific (polyclonal) radioimmunoassays. Binding assay results were, in nearly all cases, less than those measured by the nonspecific RIA and frequently greater than 20% above the values determined by the CsA-specific assays. Individual patients had pronounced differences in the relative proportions of CsA, CYP-binding (bioactive) metabolites, and cross-reacting CsA metabolites. Because the presence of bioactive metabolites may considerably contribute to the immunosuppressive activity of CsA, we consider the binding assay clinically useful for measuring CsA in biological fluids.

Administration, Oral↗
PubMed1990

Multiple infusions of human intravenous immunoglobulin in chimpanzees do not lead to immune elimination.

Administration of human i.v. immunoglobulins was shown to lead to a permanent increase in IgG1 and IgG2 levels in chimpanzees. Half-lives of human IgG1 and IgG2 in chimpanzees were comparable to those found in humans, and no signs of immune elimination were observed. Furthermore, long-term treatment of chimpanzees had no effect on the percentage of immunoregulatory T cells (CD2+, CD4+ and CD8+ T cells) as determined by FACS analysis. In addition, serum IgM levels in chimpanzees were found to be comparable to those in humans, whereas the chimpanzees' IgG levels are slightly elevated due to higher concentrations of IgG2 and, in particular, IgG4.

Animals↗
PubMed1990

Serum immunoglobulin G subclasses in patients during acute hepatitis A.

IgG subclasses were measured in sera of 47 patients with acute hepatitis A during the course of the disease. IgG1 and IgG3 serum levels were found to be elevated, whereas IgG2 and IgG4 subclass concentrations did not differ from that found in healthy control individuals. These findings indicate that, similar to the specific antiviral antibody, the polyclonal increase of serum concentrations of IgG in acute hepatitis A is not equally distributed to all IgG subclasses but is restricted to IgG1 and IgG3.

Adolescent↗
PubMed1990

[Antibody deficiency in obstructive lung diseases].

Severe chronic chest disease is the most serious complication in patients with antibody deficiency syndromes. IgG-subclass-deficiencies were a frequent finding in patients with obstructive lung disease and in patients with sinopulmonary infections. In the patient population referred to us for immunological investigation recurrent infection of the upper and lower respiratory tract was the most common reason to suspect undue susceptibility to infection. In 1034 pediatric patients analyzed 299 were found to be deficient in one of several IgG subclasses. In a group of 30 children, all of whom had severe lung disease and normal concentrations of serum IgG, IgA and IgM, airway-obstruction has been diagnosed in 19. 20 of the 30 patients had IgG-subclass-deficiency. The large percentage of IgG-subclass-deficiencies in this group of patients indicates that immunological disregulation is likely to contribute to the pathogenesis of chronic lung disease.

Adolescent↗
PubMed1988

Comparable modulation of human monocyte functions by commercial factor VIII concentrates of varying purity.

Our previous observation on immune modulation induced by a given factor VIII (F VIII) concentrate preparation was extended by showing that the immune-modulating capacity is a more general feature of F VIII products and is independent of product purity. Interaction of human monocytes with therapeutic concentrations of various F VIII concentrates (0.2 to 2 IU F VIII/mL, six different F VIII concentrates from four manufacturers) led to a significant reduction in the expression of IgG Fc receptors in the membrane of these cells (F VIII concentrate-induced downmodulation of the receptor). This Fc receptor downmodulation was achieved by a short (1-hour) incubation of human monocytes with F VIII concentrates 16 hours prior to the Fc receptor assay and did not correlate with the respective product's IgG content. Although the IgG concentrations of the different products varied greatly (from 1.0 to 177.3 mg/1,000 IU F VIII), all products behaved comparably with respect to Fc receptor downmodulation (F VIII-treated monocytes: 34% +/- 7% to 44% +/- 4% rosette-forming cells; controls in the absence of F VIII: 83% +/- 5%). Furthermore, we also were able to demonstrate that heat treatment of F VIII, now used by virtually every manufacturer to eliminate contaminating viruses, had no effect on the respective products' Fc receptor-modulating capacity. The immune-modulating component was characterized as being a high-molecular-range compound containing IgG, IgM, F VIII, and blood group substances (most likely a combination of immune complexes and immunoglobulin aggregates). This compound is present in comparable amounts in both high-purity and intermediate-purity products and apparently copurifies with F VIII during the manufacturing process.

Antigen-Antibody Complex↗
PubMed1987

Effect of UVB radiation on the biosynthesis of HLA-DR antigens.

HLA-DR molecules on the surface of immunocompetent cells are thought to represent target structures for the immunomodulating effects of UV radiation during the induction of an immune response. We therefore investigated the effect of UVB radiation on the de novo synthesis of HLA-DR-gamma-chains in the cytoplasm and the expression of alpha- and beta-chains on the surface of the human lymphoblastoid B-cell line Raji. Raji cells were UVB irradiated before biochemical experiments were performed. Cells were then metabolically labeled or radioiodinated and detergent lysates immunoprecipitated using antibodies directed against the gamma- or the alpha- and beta-chain of the HLA-DR molecule. Over a wide dose range, UVB-irradiated Raji cells were shown to still express HLA-DR determinants on their surface and, even more importantly, to be capable of synthesizing HLA-DR-alpha, beta- and gamma-chains in a normal fashion. Despite this, the functional capacity of Raji cells was impaired in a dose-dependent manner. UV radiation thus seems to exert its immunomodulating effects primarily at a different level than the incriminated immune-response-associated antigens, which are expressed as recognition structures on the surface of immunocompetent cells.

Antigen-Presenting Cells↗
PubMed1985

Human epidermal cells synthesize HLA-DR alloantigens in vitro upon stimulation with gamma-interferon.

Under certain pathologic conditions, human keratinocytes synthesize and express HLA-DR antigens. Assuming that soluble mediators might be responsible for this phenomenon, differentiating, primarily DR-keratinocytes were grown in the presence or absence of mixed leukocyte culture supernatants and tested for Ia antigen expression. After 6 days of culture, keratinocytes displayed surface-bound HLA-DR alpha/beta complexes when exposed to mixed leukocyte culture supernatants but not when cultured in media alone. These HLA-DR moieties on keratinocytes result from active biosynthesis as evidenced by the demonstration of the intracytoplasmic HLA-DR gamma (invariant) chain within these cells. In view of reports that interferon-gamma promotes Ia-production in a variety of cell types, we reasoned that this lymphokine might be responsible for the Ia-inducing property of mixed lymphocyte culture supernatants. Indeed, recombinant interferon-gamma, but not interferon-alpha or interleukin-2, proved to be a potent stimulator of Ia expression by keratinocytes. The further finding that this event can be prevented by the addition of a monoclonal anti-interferon-gamma antibody strongly suggests that this cytokine is directly responsible for HLA-DR production by keratinocytes. The interferon-gamma-induced acquisition of HLA-DR antigens by primarily DR-keratinocytes may provide a useful tool to study the role of these alloantigens in T-cell activation and may also add to our understanding of mechanisms operative in epidermal cell-T-cell interactions.

Antibodies, Monoclonal↗
PubMed1985

Expression of the Ly-5 alloantigenic system on epidermal cells.

The expression of Ly-5 alloantigens is confined to hemopoietic cell types and is therefore considered a valuable indicator for the bone marrow derivation of a given cell. The further finding that different hemopoietic cell lineages express different molecular forms of the Ly-5 alloantigens prompted us to investigate (1) whether murine epidermal cells or subpopulations thereof express Ly-5 specificities and if so, (2) whether the expression of particular molecular configurations of Ly-5 antigens would allow us to gain a clue about the derivation of certain epidermal cell populations. When epidermal sheets from BALB/c, C57Bl/6, and C3H/He mice, were exposed to monoclonal anti Ly-5.1 antibody in an indirect immunofluorescence technique, a system of evenly distributed, dendritic cells was visualized. Allelic exclusion of the Ly-5 system was demonstrated by replacing anti-Ly-5.1 antibody by anti-Ly-5.2 reagent and by using epidermal sheets from SJL/J mice. Studies on epidermal cell (EC) suspensions revealed that about 1.6-5.2% of C3H/He EC were Ly-5-reactive and that approximately equal numbers of Ly-5-positive cells bore either Thy-1 or Ia antigens. Electron microscopic studies disclosed two morphologically different Ly-5-positive cell populations, i.e., cells of the Langerhans cell lineage and a recently defined cell system, whose most prominent feature is the expression of the Thy-1 antigen. We have termed these cells dendritic Thy-1+EC (dTHY-1+EC). In order to define the molecular configurations of the Ly-5 alloantigens, EC and spleen cells were internally labeled and--after immunoprecipitation of cell-membrane detergent extracts with anti-Ly-5.1--were analyzed on sodium dodecyl sulfate-polyacrylamide gels. Spleen cells yielded 3 bands with a molecular weight of 180,000, 195,000, and 215,000, respectively, as is characteristic for T lymphocytes, non-T/non-B cells, and B lymphocytes. In contrast, a single 195,000-200,000 dalton band was found in precipitates of both untreated and Langerhans cell-depleted (anti-Ia+C) EC. These data demonstrate the existence and active biosynthesis of the Ly-5 alloantigenic system on certain EC populations, i.e., Langerhans cells and dThy-1+EC, and therefore imply that both cell types originate from a bone marrow-derived precursor. The expression of the same molecular configuration of Ly-5 alloantigens on both LC and dThy-1+EC suggest that these two cell populations do not belong either to the T-cell or to the B-cell lineage and imply an ontogenetic relationship between dThy-1+EC and Ia-positive EC.

Animals↗
PubMed1985

Inhibition of DNA synthesis of melanoma cells by azelaic acid.

Azelaic acid was successfully used in the clinical treatment of 7 cases of lentigo maligna in that remission of the lesions was observed in all our patients. In order to elucidate mechanism(s) of the beneficial clinical effects, we studied the effect of azelaic acid on cultured melanoma cells. Cell numbers recovered from melanoma cell cultures grown for several days in the presence of 10 mM azelaic acid were 50-70% less than those recovered from control cultures or from cultures containing 10 mM adipic acid. This reduction of cell numbers was not due to a simple cytotoxic or cytolytic effect of azelaic acid but rather due to a dose-dependent inhibition of DNA synthesis. Interestingly, nontoxic concentrations of azelaic acid, which significantly reduced DNA synthesis of cultured melanoma cells, had no overt effect on the protein synthesis of these cells. It is conceivable that inhibition of DNA synthesis is one of the mechanisms by which azelaic acid prevents growth and proliferation of abnormal melanocytes.

Administration, Topical↗