Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy

Abstract

Like in many fields of medicine, the concept of precision dosing has re-emerged in routine practice in allergology. Only one retrospective study on French physicians' practice has addressed this topic so far and generated preliminary data supporting dose adaptation, mainly based on experience, patient profile understanding and response to treatment. Both intrinsic and extrinsic factors shape the individual immune system response to allergen immunotherapy (AIT). Herein, we focus on key immune cells (i.e., dendritic cells, innate lymphoid cells, B and T cells, basophils and mast cells) involved in allergic disease and its resolution to further understand the effect of AIT on the phenotype, frequency or polarization of these cells. We strive to discriminate differences in immune responses between responders and non-responders to AIT, and discuss the eligibility of a non/low-responder subset for dose adaptation. A differential behavior in immune cells is clearly observed in responders, highlighting the importance of conducting clinical trials with large cohorts of well-characterized subjects to decipher the immune mechanism of AIT. We conclude that there is a need for designing new clinical and mechanistic studies to support the scientific rationale of dose adaptation in the interest of patients who do not properly respond to AIT.

Keywords: T cells; allergen immunotherapy; basophils; biomarkers; clinical response; determinants; dose adaptation; immune response; innate lymphoid cells; precision dosing.

Figure 1

Mechanisms of allergic inflammation (in case of natural allergen exposure) and of immunological and clinical tolerance (in case of precision dosing during AIT)—Figure adapted from [3] with permission from Elsevier. Stars represent a given allergen. Breg, Regulatory B cell; DC, Dendritic cell; CCL, Chemokine ligand; CD, Cluster of differentiation; CTLA-4, Cytotoxic T-lymphocyte-associated protein 4; FcεRI, Type I Fcε receptor; IFN-γ, Interferon γ; Ig, Immunoglobulin; IgE-FAB, IgE-facilitated allergen binding; IL, Interleukin, ILC2, Group 2 innate lymphoid cell; iT_R35, IL-35-producing Treg; PC, Plasma cell; PD-L1, Programmed death-ligand 1; TGF-β, Transforming growth factor β; T_H, T helper; T_R1, Type 1 Treg; Treg, Regulatory T cell; TSLP, Thymic stromal lymphopoietin.