Omalizumab treatment downregulates dendritic cell FcepsilonRI expression.

Abstract

BACKGROUND:

Dendritic cells (DCs) are potent antigen-presenting cells that express FcepsilonRI, the high-affinity IgE receptor. Although the downregulation of basophil FcepsilonRI during anti-IgE therapy with omalizumab is well documented, its effect on FcepsilonRI expression by DCs has not been reported.

OBJECTIVE:

We hypothesized that IgE regulates surface FcepsilonRI expression by DCs in vivo and that, consequently, anti-IgE therapy decreases FcepsilonRI expression by DCs.

METHODS:

In a randomized, double-blind, placebo-controlled clinical trial 24 subjects (16 receiving omalizumab and 8 receiving placebo) with seasonal allergic rhinitis received the study drug on days 0 and 28. Serial blood samples drawn on days 0, 7, 14, 28, and 42 were analyzed for precursor DC1 (pDC1) and pDC2 surface expression of FcepsilonRIalpha by using flow cytometry.

RESULTS:

Omalizumab caused a significant decrease in surface FcepsilonRI expression at all time points examined in both the pDC1 and pDC2 subsets. No significant change was seen with placebo. The maximum decrease in FcepsilonRI expression in the omalizumab group was 52% and 83%, respectively, for the pDC1 and pDC2 subsets. The decrease in FcepsilonRI expression by both pDC subsets correlated with the decrease in serum-free IgE and was of a similar magnitude to that found in basophils. A 10-fold decrease in IgE corresponded to a 42% and 54% decrease in surface FcepsilonRI expression by the pDC1 and pDC2 subsets, respectively.

CONCLUSION:

These results demonstrate that anti-IgE therapy causes a rapid decrease in DC surface FcepsilonRI expression and establish that IgE is an important regulator of FcepsilonRI expression by DCs.

• Authors: Calman Prussin, Daniel T Griffith, Kevin M Boesel, Henry Lin, Barbara Foster, Thomas B Casale
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 112 Issue 6 Pg. 1147-54 (Dec 2003) ISSN: 0091-6749 [Print] United States
• PMID: 14657874 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anti-Idiotypic
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Receptors, IgE
• anti-IgE antibodies
• Omalizumab
• Immunoglobulin E

Topics

• Adult
• Ambrosia (adverse effects, immunology)
• Antibodies, Anti-Idiotypic (administration & dosage, therapeutic use)
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Dendritic Cells (immunology, metabolism)
• Double-Blind Method
• Down-Regulation
• Flow Cytometry
• Humans
• Immunoglobulin E (blood, immunology)
• Middle Aged
• Omalizumab
• Receptors, IgE (metabolism)
• Rhinitis, Allergic, Seasonal (drug therapy, etiology)
• Treatment Outcome