Omalizumab enhances the percentage of GARP cells in both regulatory and terminally differentiated effector Th cells in severe allergic asthmatics

In 2003, FDA approved Omalizumab for the treatment of severe allergic asthma. This mAb recognizes IgE and blocks its binding to basophils and mast cells, attenuating FceRI signalling. Nevertheless, its effect on T helper (Th) subsets like regulatory (Tregs) or effector (Teff) cells remains poorly described. To address this issue peripheral blood samples were drawn from three groups of adults (n= 106): Healthy controls (HC; n= 32) and clinically stable allergic asthmatics (n= 74), either on glucocorticoid (Omalizumab-; n= 50) or Omalizumab (Omalizumab+; n= 24) therapy. Due to the higher severity in the Omalizumab+ group and despite the biological, FEV1 (%) and FEV1/FVC (%) were still lower than those in Omalizumab- patients. Asthmatics showed higher eosinophil numbers and total IgE compared to HC, but Omalizumab did not cause their down-modulation. Flow cytometry evidenced a higher activated status (CD26) in Th cells from asthmatics that was not affected by Omalizumab. In contrast, the increment of “terminally differentiated” Teff percentages in Omalizumab- patients compared to HC was almost lost in the Omalizumab+ group. The biological therapy did not alter the percentage of circulating Treg cells or levels of serum TGFβ1 but led to a significant increment in the percentage of GARP+ cells within Treg and “terminally differentiated” Teff compared to HC. GARP is a receptor for latent TGFβ1 and a Treg activation marker. Therefore, apart from the actions of Omalizumab on mast cells and basophils, an additional mechanism could be the generation of lymphocytes with enhanced regulatory function or higher susceptibility to this activity.