Dupilumab: Advances in the off‐label usage ofIL4/IL13antagonist in dermatoses

Abstract

Type 2 immune response refers to a complicated series of immune responses characterized by Th2 polarization and Th2 cytokines secretion. The IgE secretion, airway hypersensitivity, and effector cell recruitment (eosinophils, mast cells, basophils) in skin lesion and peripheral blood stream could be upregulated during the activation of type 2 immune response. Th1/Th2 ratio, also referred as Th1/Th2 balance, represent the T lymphocytes immune pattern to a certain degree: Th1-dominated responses are often involved in intracellular infections (e.g., mycobacterium tuberculosis) and autoimmune diseases (e.g., Graves' disease) while Th2-dominated responses are involved in allergic conditions (e.g., atopic dermatitis, eczema), IgE mediated diseases (e.g., urticaria), and fibrotic dermatoses (e.g., keloids). Dupilumab, as one of the most widely applied Th2 cytokine inhibitors, could block the bioactivity of IL-14/IL-13 via competitively binding to the common IL-4Rα subunit shared by IL-4 and IL-13 receptors. In addition to the direct inhibition of type 2 response, dupilumab is also effective in autoimmune and some infectious skin diseases through indirect regulation of type 1 immune response. The pathological mechanism of Th2 responses and advanced clinical application of dupilumab in skin diseases will be summarized and discussed in the review.

Hidradenitis suppurativa presents a methylome dysregulation capable to explain the pro‐inflammatory microenvironment: Are these DNA methylations potential therapeutic targets?

“…Furthermore, this concept is also sustained by IL‐4/13 signaling impairement that we detected with REACTOME, a classic sign of barrier dysfuntion (i.e. atopic dermatitis 74 ) and dysbiosis 75 . No data are present at the moment regarding the use of IL‐4/IL‐13 or even IL‐13 antagonists on HS.…”

Pharmacotherapy for Keloids and Hypertrophic Scars

“…Since IL-4 and IL-13 play important roles in the pathogenesis of allergic diseases, blocking both the IL-4 and IL-13 signals is a powerful and effective strategy for treating allergic diseases. Dupilumab (Dupixent ® ) is a fully human monoclonal antibody that recognizes IL-4Rα and blocks both the IL-4 and IL-13 signals [195][196][197][198][199]. In clinic, a patient with numerous disfiguring HTSs or KDs after suffering from a severe herpes zoster infection was treated with dupilumub orally, and many scars flattened, but several scars further developed.…”

Basophils in pruritic skin diseases

“…The pro-inflammatory effect of basophils in AD might be reduced by treatment with dupilumab. The monoclonal IgG4 antibody, which binds to IL-4Rα, showed success in reducing symptoms, such as itch, of AD patients ( 71 ). Since the antibody binds to IL-4Rα, the assumption arises, that the cytokines which contribute to the disease are partially derived from basophils ( 71 ).…”

“…The monoclonal IgG4 antibody, which binds to IL-4Rα, showed success in reducing symptoms, such as itch, of AD patients ( 71 ). Since the antibody binds to IL-4Rα, the assumption arises, that the cytokines which contribute to the disease are partially derived from basophils ( 71 ). Aside from their pro-inflammatory properties, basophils can aid in the resolution of AD.…”