Against all odds: anti-IgE for intrinsic asthma?

Abstract

For many years, pathogenetic concepts and the results of clinical trials supported the view that anti-IgE treatment is specifically effective in allergic asthma. However, there is now growing clinical and mechanistic evidence suggesting that treatment with the anti-IgE antibody omalizumab can be effective in patients with intrinsic asthma. Therefore, large and well-controlled clinical trials with anti-IgE are urgently warranted in patients with intrinsic asthma. In addition, there is a need to find new biomarkers which can identify patients with asthma who respond to anti-IgE treatment.

Keywords: Asthma; Asthma Mechanisms; Asthma Pharmacology.

Figure 1

Possible mechanisms of anti-IgE treatment in intrinsic asthma. One hypothesis assumes that patients with intrinsic asthma have a localised allergy with elevated concentrations of allergen-specific IgE antibodies in the airways. In this scenario, anti-IgE treatment would reduce local allergic inflammation in the airways, leading to a reduction in disease severity and exacerbation rates. Another hypothesis assumes that plasmacytoid dendritic cells (pDCs) of patients with intrinsic asthma are characterised by an immunological imbalance: enhanced cross-linking of the high-affinity IgE receptor on pDCs suppresses anti-viral activity of these cells. In this scenario, viral infections could trigger intrinsic asthma. Anti-IgE treatment would reduce serum IgE concentrations and IgE receptors on pDCs, and restore the anti-viral activity of pDCs—resulting in reduced disease severity and reduced exacerbation rates.