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    We have cared for an unusual patient with serum IgE concentrations of up to 150,000 IU/mL who did not have the hyper-IgE syndrome.Our objective in this study was to compare the regulation of in vitro IgE synthesis in this patient with results reported for in vitro IgE production by patients with the hyper-IgE syndrome.We utilized an enzyme-linked immunosorbent assay to measure in vitro IgE production under varying conditions. In vitro cytokine production including IL-2, IL-4, IL-6, and interferon-gamma also was evaluated as was expression of the IgE receptor molecule CD23.B cells from this patient produced high concentrations of IgE. The patient was found to produce very high levels of interleukin-4 (IL-4) in vitro, to have high levels of soluble CD23 in his serum, and to have cells that were inconsistently responsive to the effect of IL-4 on IgE synthesis.Patients with elevated production of IL-4 may have increased serum IgE concentrations without having the hyper-IgE syndrome syndrome.
    CD23
    Citations (2)
    IgE fragments were detected by polyclonal and monoclonal anti-IgE antibodies using Western blot techniques and immunoassays. Other antibodies detected only intact IgE molecules. In the presence of IgE fragments, higher IgE levels were estimated, depending on the epitope specificity of the antibodies used in the IgE determination assays. IgE fragments have been found together with intact IgE in isolated material from different human sera and also from culture supernatant of an IgE-producing cell line. Our data demonstrate that IgE fragments may be assessed and represent a potential pitfall in diagnostic IgE determinations.
    Polyclonal antibodies
    Citations (10)
    Abstract. We fractionated, by gel chromatography, sera with high IgE content from atopic subjects and five cases with the hyper‐lgE syndrome, and measured the presence of IgE in high molecular weight (HMW) fractions. Two out of four asthmatics and four out of five hyper‐IgE had HMW IgE. The same serum fractions gave positive results for conglutinin binding IgG (all six) and IgA (three cases) as well as C1q binding complexes (five cases). IgG auto‐antibodies to IgE were also detected together with IgE in HMW fractions. Anti‐F(ab)' 2 activity was present in five cases (one of them negative for IgG anti‐IgE). Our data indicate that complexes made of IgE and IgG anti‐IgE are present mainly in patients with chronic allergic symptoms and most frequent in cases of hyper‐IgE syndrome.
    IgE antibodies play a crucial role in allergic type I reactions. Only IL-4 and IL-13 are able to induce an immunoglobulin isotype switch to IgE in B cells. A major question is to what extent these cytokines contribute to the production of IgE in allergic patients. To address this question we used an in vitro culture system in which the production of IgE is dependent on endogenously produced IL-4 and IL-13. In cultures of purified T and B cells from allergic asthma patients and non-atopic controls, T cells were polyclonally stimulated to obtain IL-4, IL-13 and subsequently IgE secretion. The absolute amount of IgE produced was not significantly different between patients and controls. When neutralizing IL-4 antibodies were included during culture, the production of IgE was dramatically inhibited in both patients and controls (production of IgE was reduced to 12%). However, neutralization of IL-13 led to a significantly stronger inhibition of IgE production in the patient group: production of IgE was reduced to 23 +/- 3% versus 50 +/- 10% in the control group. Corresponding with these results, we also observed a higher production of IL-13 by the patients, while the production of IL-4 was not significantly different. A more detailed analysis of the production of IL-13 revealed that patients' T cells were less sensitive to a negative signal controlling IL-13 production. Our results indicate that, at least in vitro, IgE production in allergic asthma patients is more dependent on IL-13 than in non-atopics, due to enhanced IL-13 production and to enhanced IgE production in response to IL-13.
    Isotype
    Interleukin 13
    The levels of total IgE and IgE antibodies to mite per unit quantity of nasal fluid were successfully determined by our special method of collecting nasal fluid. The mean value of IgE was 80 ± 101 U/ml, and that of IgE Ab 1.45 ± 1.29/ml (RAST score) in NF. Nasal IgE concentration was approximately one twenthieth of serum IgE on the average, and nasal IgE Ab to mite was one half of serum IgE. The IgE Ab/IgE ratio was nine times greater in NF (0.0181) than in serum (0.0022). The concentration of IgE Ab to mite was very well correlated between serum and NF (correlation coefficient of 0.83), while that of IgE was not (coefficient of 0.51). IgE Ab to mite was also well correlated to IgE (coefficient of 0.78) in NF while it was not in serum (coefficient of 0.48). The correlation coefficient of nasal/serum IgA was 0.41; that of IgE/IgA in NF was 0.31; and that of IgE/total protein in NF was also 0.31. The possibility of local production and secretion of IgE Ab to specific allergen is discussed in detail.
    Citations (19)