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Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma

Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma
Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma
IgE plays an important role in allergic asthma. We hypothesized that reducing IgE in the airway mucosa would reduce airway inflammation. Forty-five patients with mild to moderate persistent asthma with sputum eosinophilia of 2% or more were treated with humanized monoclonal antibody against IgE (omalizumab) (n = 22) or placebo (n = 23) for 16 weeks. Outcomes included inflammatory cells in induced sputum and bronchial biopsies, and methacholine responsiveness. Treatment with omalizumab resulted in marked reduction of serum IgE and a reduction of IgE+ cells in the airway mucosa. The mean percentage sputum eosinophil count decreased significantly (p < 0.001) from 6.6 to 1.7% in the omalizumab group, a reduction significantly (p = 0.05) greater than with placebo (8.5 to 7.0%). This was associated with a significant reduction in tissue eosinophils; cells positive for the high-affinity Fc receptor for IgE; CD3+, CD4+, and CD8+ T lymphocytes; B lymphocytes; and cells staining for interleukin-4, but not with improvement in airway hyperresponsiveness to methacholine. This study shows antiinflammatory effects of omalizumab treatment and provides clues for mechanisms whereby omalizumab reduces asthma exacerbations and other asthma outcomes in more severe asthma. The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma.
eosinophils, high-affinity Fc receptor for IgE, Fc{epsilon}RI, interleukin-4
1073-449X
583-593
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Kraft, Monica
161231c7-9056-42d9-92e1-fcfec799cafa
Jarjour, Nizar N.
0692f64d-7331-446a-8abd-ed98e9ff31fd
Steel, Mark
9aba70fc-b892-4571-8fd4-df6aeaf624fa
Chung, K. Fan
c4808f91-e1eb-4b84-9389-803e710dd1ab
Bao, Weibin
26dbed99-7496-4f4a-b8ef-9bed8f1f163f
Fowler-Taylor, Angel
022aa58b-e333-4ede-ad75-246643ba68d7
Matthews, John
8a4b647b-1b7d-452b-8e00-4937c47900c1
Busse, William W.
ce4badff-37c5-43ca-a199-dd130d929932
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Fahy, John V.
28d57b70-d25e-4484-9015-c9ba2bcd0505
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Kraft, Monica
161231c7-9056-42d9-92e1-fcfec799cafa
Jarjour, Nizar N.
0692f64d-7331-446a-8abd-ed98e9ff31fd
Steel, Mark
9aba70fc-b892-4571-8fd4-df6aeaf624fa
Chung, K. Fan
c4808f91-e1eb-4b84-9389-803e710dd1ab
Bao, Weibin
26dbed99-7496-4f4a-b8ef-9bed8f1f163f
Fowler-Taylor, Angel
022aa58b-e333-4ede-ad75-246643ba68d7
Matthews, John
8a4b647b-1b7d-452b-8e00-4937c47900c1
Busse, William W.
ce4badff-37c5-43ca-a199-dd130d929932
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Fahy, John V.
28d57b70-d25e-4484-9015-c9ba2bcd0505

Djukanovic, Ratko, Wilson, Susan J., Kraft, Monica, Jarjour, Nizar N., Steel, Mark, Chung, K. Fan, Bao, Weibin, Fowler-Taylor, Angel, Matthews, John, Busse, William W., Holgate, Stephen T. and Fahy, John V. (2004) Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. American Journal of Respiratory and Critical Care Medicine, 170 (6), 583-593. (doi:10.1164/rccm.200312-1651OC).

Record type: Article

Abstract

IgE plays an important role in allergic asthma. We hypothesized that reducing IgE in the airway mucosa would reduce airway inflammation. Forty-five patients with mild to moderate persistent asthma with sputum eosinophilia of 2% or more were treated with humanized monoclonal antibody against IgE (omalizumab) (n = 22) or placebo (n = 23) for 16 weeks. Outcomes included inflammatory cells in induced sputum and bronchial biopsies, and methacholine responsiveness. Treatment with omalizumab resulted in marked reduction of serum IgE and a reduction of IgE+ cells in the airway mucosa. The mean percentage sputum eosinophil count decreased significantly (p < 0.001) from 6.6 to 1.7% in the omalizumab group, a reduction significantly (p = 0.05) greater than with placebo (8.5 to 7.0%). This was associated with a significant reduction in tissue eosinophils; cells positive for the high-affinity Fc receptor for IgE; CD3+, CD4+, and CD8+ T lymphocytes; B lymphocytes; and cells staining for interleukin-4, but not with improvement in airway hyperresponsiveness to methacholine. This study shows antiinflammatory effects of omalizumab treatment and provides clues for mechanisms whereby omalizumab reduces asthma exacerbations and other asthma outcomes in more severe asthma. The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma.

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More information

Published date: 2004
Keywords: eosinophils, high-affinity Fc receptor for IgE, Fc{epsilon}RI, interleukin-4

Identifiers

Local EPrints ID: 27025
URI: https://eprints.soton.ac.uk/id/eprint/27025
ISSN: 1073-449X
PURE UUID: c6c32e48-621c-48d5-8569-242fed4807e2
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 24 Apr 2006
Last modified: 29 Jun 2018 00:36

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