The Role of T Helper Type 2 (Th2) Cytokines in the Pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (eGPA): an Illustrative Case and Discussion

• Published in: Current allergy and asthma reports Vol. 22; no. 11; pp. 141 - 150
• Main Authors: Milne, Megan E., Kimball, Jack, Tarrant, Teresa K., Al-Rohil, Rami N., Leverenz, David L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2022; Springer Nature B.V
• Subjects: Allergology; Cytokines; Immunotherapy and Immunomodulators (B Vickery; Immunotherapy and Immunomodulators (B Vickery, Section Editor); Inflammatory diseases; Medicine; Medicine & Public Health; Pathogenesis; Section Editor; Topical Collection on Immunotherapy and Immunomodulators; Vein & artery diseases; IL-4; IL-5; IL-13; Th2 inflammatory response; Eosinophilic granulomatosis with polyangiitis
• ISSN: 1529-7322; 1534-6315
• DOI: 10.1007/s11882-022-01039-w

Purposeof Review The pathogenesis of eosinophilic granulomatosis with polyangiitis (eGPA) is driven largely by CD4 + type 2 helper T cells (Th2), B cells, and eosinophils. Interleukin (IL)-4 and IL-13 are critical cytokines in Th2 cell–mediated inflammation; however, inhibition of IL-4 and IL-13 does not reduce serum eosinophil counts and has even been associated with hypereosinophilia. This review explores the role of IL-4, IL-5, and IL-13 in Th2-mediated inflammation to consider the potential clinical consequences of inhibiting these individual cytokines in eGPA. Recent Findings Treatments for eosinophilic granulomatosis with polyangiitis (eGPA) are rapidly evolving through using biologic therapies to modulate the Th2 inflammatory response via eosinophil inhibition. While IL-4, IL-5, IL-13, and IL-25 can all affect eosinophils, only IL-5 inhibition has demonstrated therapeutic benefit to-date. In this review, we report a clinical vignette of a patient with adult-onset asthma who developed severe manifestations of eGPA after switching from mepolizumab (an IL-5 inhibitor) to dupilumab (an inhibitor of IL-4 and IL-13). Summary By understanding the role of IL-4, IL-5, and IL-13 in Th2-mediated vasculitis, we can start to understand how eGPA might respond differently to focused cytokine inhibition.