Abstract
BackgroundOmalizumab, is a humanized anti-IgE monoclonal antibody used to treat allergic asthma. Decreased serum IgE levels, lower eosinophil and B cell counts have been noted as a result of treatment. In vitro studies and animal models support the hypothesis that omalizumab inhibits IgE synthesis by B cells and causes elimination of IgE-expressing cells either by induction of apoptosis or induction of anergy or tolerance.MethodsWe examined the influence of omalizumab on human tonsillar B cell survival and on the genes involved in IgE synthesis. Tonsillar B cells were stimulated with IL-4 plus anti-CD40 antibody to induce class switch recombination to IgE production in the presence or absence of omalizumab. Cell viability was assessed and RNA extracted to examine specific genes involved in IgE synthesis.ConclusionsWe found that omalizumab reduced viable cell numbers but this was not through induction of apoptosis. IL-4R and germline Cϵ mRNA levels were decreased as well as the number of membrane IgE+ cells in B cells treated with omalizumab. These data suggest that omalizumab may decrease IgE synthesis by human B cells by specifically targeting membrane IgE-bearing B cells and inducing a state of anergy.
Highlights
Omalizumab, is a humanized anti-IgE monoclonal antibody used to treat allergic asthma
Omalizumab reduced the number of membrane IgE+ B cells The combination of IL-4 plus anti-CD40 is known to induce class switching to secretion of IgE by human B cells [11,12]
To determine if omalizumab influenced the ability of IL-4 plus anti-CD40 to induce B cells to synthesize IgE, B cells were evaluated by flow cytometry for the number of membrane IgE+ cells after treatment for 4 days with IL-4 plus anti-CD40 in the presence or absence of omalizumab
Summary
Omalizumab, is a humanized anti-IgE monoclonal antibody used to treat allergic asthma. Decreased serum IgE levels, lower eosinophil and B cell counts have been noted as a result of treatment. Direct correlations have been noted between asthma and serum IgE levels [1]. The antibody should not bind to IgE bound to either the high affinity or low affinity IgE receptor. Omalizumab (Xolair®; Genentech/ Novartis) is a recombinant humanized monoclonal antiIgE IgG1 kappa antibody used in the treatment of allergic asthma. Omalizumab binds free IgE in serum and membrane-expressed IgE on B cells [2]. Administration of omalizumab either intravenously or subcutaneously significantly reduced serum levels of IgE and asthmatic symptoms [3,4,5]
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