Anti-IgE (omalizumab) inhibits late-phase reactions and inflammatory cells after repeat skin allergen challenge.
BACKGROUND
Anti-IgE (omalizumab) inhibited early and late asthmatic reactions and infiltration of inflammatory cells in asthmatic bronchial biopsies at baseline. The effect of chronic allergen exposure on these outcomes is unknown. Repeat allergen challenge in human skin represents a suitable model to address this question.


OBJECTIVE
To study the effect of anti-IgE (omalizumab) on early-phase (EPR) and late-phase (LPR) skin reactions and cellular infiltration by using a repeat skin allergen challenge designed to imitate chronic allergen exposure.


METHODS
Twenty-four atopic allergic volunteers received omalizumab or placebo for 12 weeks. Paired intradermal challenges of allergen (30 biological units) and diluent control were administered on 9 occasions at 2-week intervals. Early-phase and late-phase skin reactions and cellular infiltration in skin biopsies (using immunohistochemistry and in situ hybridization) were measured at intervals.


RESULTS
Compared with placebo, omalizumab-treated patients had a progressive reduction in the LPR that was significantly greater than its effect on the EPR (median, --63% vs--24% respectively; P=.009). In addition, significant reduction of the LPR was reached within 2 weeks of commencing treatment, compared with 8 weeks for the EPR. There was a priming effect of repeated allergen challenge on infiltration of eosinophil, neutrophil, T(H)2 (CD3(+)/IL-4(+)), and total FcepsilonRI(+) cells in patients on placebo that was abrogated in those receiving omalizumab.


CONCLUSIONS
The more marked effect of omalizumab on the LPR and prevention of the repeat-dose priming effect on several inflammatory cell types support a role for anti-IgE treatment in conditions associated with chronic allergic inflammation.
Ong
Yee Ean
YE
Department of Allergy and Clinical Immunology, Imperial College London, National Heart and Lung Institute, South Kensington, London, UK.
Menzies-Gow
Andrew
A
Barkans
Julia
J
Benyahia
Farid
F
Ou
Tsen-Teng
TT
Ying
Sun
S
Kay
A Barry
AB
D000328:Adult; D000485:Allergens / Q000276:immunology; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000188:drug therapy*; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D000069444:Omalizumab; D012867:Skin / Q000166:cytology / Q000276:immunology; D012882:Skin Tests; D013997:Time Factors
D000485:Allergens; D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C026408:anti-IgE antibodies; D000069444:Omalizumab; D007073:Immunoglobulin E