Low Immunoglobulin E Research Articles

Studies on the immunoglobulin-E system of the common marmoset in comparison with human data

In the common marmoset ( Callithrix jacchus jacchus) immunoglobulin E (IgE) serum levels and IgE synthesis of peripheral blood mononuclear cells (PBMC) in vitro were investigated in order to look for homologies to the human system. While IgE was not found in marmoset blood plasma with three commercial antihuman IgE-kits with monoclonal antibodies (mAbs), two other kits using polyclonal antibodies against human IgE revealed detectable IgE concentrations of up to 10 kU/liter in plasma samples of 19 out of 21 marmosets. In accord with human data, rhIL-4 showed biological functions under in vitro conditions in PBMC of the New World monkey. Proliferation, measured by 3H-thymidine incorporation, of isolated PBMC of marmosets could be induced by rhIL-4. FACScan analysis showed an enhanced expression of the low affinity IgE receptor CD23 (FcεRII) on CD20 + B lymphocytes after incubation with rhIL-4. Furthermore, PBMC from marmosets could be stimulated by IL-4 alone or in combination with dexamethasone as well as with lipopolysaccharide (E. coli) to produce IgE in culture. The results indicate that Callithrix jacchus is using an IgE system that is rather similar to that of humans, although not completely identical. Antihuman mAbs and rhIL-4 can be used to investigate IgE regulation in vitro of marmoset PBMC. These data encourage the development of a primate animal model for studying possible modifications of the IgE system under pathological conditions to find new therapeutic strategies in atopic diseases.

Centrifugation assay of IgE‐mediated cell adhesion to antigen‐coated gels

AbstractThe adhesion of biological cells to substrates is often mediated by binding between cellular receptors and substrate‐bound ligand. In this work, we used a centrifugation assay to measure the adhesion of rat basophilic leukemia (RBL) cells coated with immunoglobulin E (IgE) to substrates coated with the ligand dinitrophenol (DNP). Increasing force, decreasing DNP substrate density, and decreasing cell surface IgE density all led to decreasing adhesion. Experiments performed at low IgE cell surface densities, in which few tethers from between cell and substrate suggest individual tethers have a binding strength of 2 to 4 microdyne, in agreement with previous measurements of the force to uproot receptors from the plasma membrane. We use this system to show how subpopulations expressing different numbers of cell surface receptors may be separated by exploiting their differential adhesiveness to substrates.

Expression of functional high affinity immunoglobulin E receptors (Fc epsilon RI) on monocytes of atopic individuals.

Suggestive evidence indicates that immunoglobulin E (IgE)-dependent activation of mononuclear phagocytes plays an important pathogenic role in allergic tissue inflammation. Prevailing opinion holds that low affinity IgE receptors are the relevant IgE-binding structures on monocytes/macrophages and that functional events occurring after cross-linking of membrane-bound IgE on these cells are mediated by these receptors. Here we demonstrate that peripheral blood monocytes can bind monomeric IgE via the high affinity IgE receptor (Fc epsilon RI) and that Fc epsilon RI expression on these cells is upregulated in atopic persons. Further, we demonstrate that, upon monocyte adherence to substrate, bridging of monocyte Fc epsilon RI is followed by cell activation. We propose that direct interaction of multivalent allergen with Fc epsilon RI(+)-bound IgE on mononuclear phagocytes results in cell signaling via Fc epsilon RI and that the biological consequences of this event may critically influence the outcome of allergic reactions.

Structure and function of the low affinity IgE receptor.

Signal transduction through cell surface receptors such as those specific for antigen, lymphokines or immunoglobulin (Ig) is an important event for many facets of cell growth and differentiation. The group of receptors which interact with the Fc region of Ig are involved in a number of immune functions, including phagocytosis, antibody dependent cellular cytotoxicity and release of inflammatory mediators (see1 for review). The Fc receptors that interact with immunoglobulin E (IgE) have been divided into two predominant receptors. Fc ∈ RI, or the high affinity receptor for IgE, is found predominantly on mast cells and basophils and is involved in cytokine and allergic mediator release from these cellsl. Discovered somewhat later, the Fc ∈ RII, or the low affinity receptor for IgE, is expressed on a wide variety of hematopoietic cell types. The finding that the Fc ∈ RII was synonymous with the B cell differentiation antigen CD232,3 led to a merging of two areas of investigation for this protein; the study of the role of the Fc ∈ RII/CD23 (the names are used interchangeably) in B cell activation/differentiation and the study of the role of the Fc ∈ RII in IgE production. This review chapter will concentrate on summarizing recent developments regarding the Fc ∈ RII with regard to both the structure and function of this molecule. Several other recent reviews on this subject are also available4–6.KeywordsSoluble CD23Lectin DomainComplement Receptor TypeHematopoietic Cell TypeRecombinant Soluble CD23These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Serum IgE levels in adults with asthma.

Serum total immunoglobulin E (IgE) was measured in 88 normal adults and 100 adults with asthma using Phadebas IgE PRIST kits. The geometric mean IgE in our normal subjects was found to be higher than that reported by some investigators but was similar to or lower than that reported by others without showing any geographic pattern. It increased progressively from 92 kU/L in normal controls through 205 kU/L in cases of asthma with low atopic scores to 464 kU/L in asthma cases with high atopic scores. There was wide variation in IgE levels among individuals, making it difficult to use it to classify any subject into one of these groups. However, as a group, female asthmatics had lower mean IgE levels (182 kU/L) than did men (577 kU/L), and a higher proportion of them had low atopic scores (60% of the women versus 47% of the men). This suggests that probably more women had intrinsic asthma, while extrinsic asthma was more common among men in the population studied.

Immunoglobulin E antibody production against house dust mite, Dermatophagoides farinae, in mice.

Immunoglobulin E (IgE) antibody production against Dermatophagoides farinae extract (mite antigen) was studied in female BALB/c mice. When mice were immunized with mite antigen and aluminium hydroxide gel (alum) intraperitoneally at intervals of 30 d, good primary, secondary and tertiary IgE antibody responses were observed. In the absence of adjuvant, a subcutaneous injection of mite antigen failed to induce the primary IgE antibody response. However, good IgE antibody responses were observed after the secondary immunization given 30 d after the primary immunization. Furthermore, 5 weekly injections of mite antigen alone also induced the IgE antibody production. Intranasal administrations of mite antigen alone also induced the IgE antibody production in mice. Two exposures to mite antigen, intranasally, were sufficient for eliciting low IgE antibody production. The response was significantly potentiated by the administration of islet-activating protein obtained from culture fluids of Bordetella pertussis. These results indicate that the intranasal administration of mite antigen is very effective for eliciting the IgE antibody production.

CIRCULATING LEVELS OF IMMUNOGLOBULIN E IN PATIENTS WITH CANCER

Circulating levels of immunoglobulin E (IgE) have been determined by solidphase radioimmunoassay and by radial immuno-diffusion technique in healthy controls and in a large group of patients with advanced cancer. The mean level in the control group, as determined by radioimmunoassay, was 215 units per ml. (range 85-740). In patients receiving cytotoxic drugs, the mean level was significantly lower, and most had values below the normal range. Similar findings were obtained in approximately half the patients with advanced, untreated neoplasms, and there was a close correlation between the results obtained by the two assays in the controls and in these cancer patients. Conversely, the remaining patients with untreated neoplasms had low or undetectable IgE levels as determined by radial immunodiffusion, but apparently very high values (usually more than 100,000 units per ml.) by radioimmunoassay. Additional studies indicated that the high immunoreactive levels were an artefact due to the presence of a circulating inhibitor.