Rl. Miller et al., ANALYSIS OF CYTOKINE SIGNALING IN PATIENTS WITH EXTRINSIC-ASTHMA AND HYPERIMMUNOGLOBULIN-E, Journal of allergy and clinical immunology, 102(3), 1998, pp. 503-511
Background: Recent data suggest that the regulation of class switching
to IgE by cytokines is mediated by STAT transcription factors. The in
duction of IgE by IL-4 and IL-13 occurs through the activation of the
intracellular signal-transducing protein Stat6, whereas the inhibition
of IgE class switching by interferon-gamma (IFN-gamma occurs through
the activation of Stat1. Objective: We hypothesized that in extrinsic
asthma or in cases of markedly elevated IgE tie, hyperimmunoglobulin E
[HIE]) increased levels of IgE may be associated with alterations in
the cytokine levels or the activation of Stat6, Methods: PBMCs and ser
a from 8 patients with extrinsic asthma (mean IgE, 285 +/- 100 IU/mL),
3 patients with HIE (mean IgE, 7050 +/- 1122 IU/mL), and 14 nonatopic
control subjects (mean IgE, 112 +/- 28 IU/mL) were analyzed. Results:
The mean IL-4 level detected by ELISA was much greater in patients wi
th HIE than control subjects (88.6 +/- 11.5 pg/mL vs 11.5 +/- 7.1 pg/m
L, P =.005), and increased IL-4 levels among patients with both asthma
and HIE correlated with the increased IgE levels, In contrast, IL-13
levels were not elevated. Levels of Stat6 protein present in PBMCs did
not differ in the patients and control subjects. Examination of Stat6
DNA-binding activity demonstrated no activation of IL-4 signaling in
patients with either HIE or acute asthma, Interestingly, evidence for
the presence of B cells that have already switched to IgE was seen in
PBMCs of several patients with asthma or HIE. Conclusion: These result
s indicate that (1) IgE production in asthma and HIE usually is associ
ated with elevated levels of IL-4, but not IL-13, in the peripheral bl
ood; (2) the increased sera IL-4 levels in asthma and HIE are not suff
icient to induce Stat6 activation in PBMCs; and (3) evidence of switch
recombination to E may be detected in isolated cases of elevated IgE,
This implies that high levels of IgE in these patients either results
from B cells that have already undergone class switching, from Ig cla
ss switching that is localized to target tissues, or both.