[Different immunological types of CRSwNP in the context of the new European EAACI nomenclature : Part 2: Hypersensitivity reactions of type V (epithelial barrier defects)].

backgroundChronic rhinosinusitis (CRS) has a prevalence of up to 11% in Europe and the United States, making it one of the most common chronic diseases. Classification according to immunological endotypes is increasingly being incorporated into disease definitions, particularly for chronic rhinosinusitis with nasal polyps (CRSwNP). Genetic and epigenetic alterations within the mucosal immune system play an important role in this context. Identification of endotypes may help to elucidate disease heterogeneity and guide development of personalized therapeutic approaches. In part 1 of this publication series, we presented the immunological classification of type IV hypersensitivity reactions (T1, T2, and T3 endotypes).

methodsThe European Academy of Allergy and Clinical Immunology (EAACI) recently published a position paper introducing the updated nomenclature for immunological hypersensitivity reactions based on nine distinct immunological reaction types. The antibody-mediated reactions originally classified by Coombs and Gell as type I, type II, and type III have been expanded and described in greater detail. Epithelial barrier defects are defined as type V hypersensitivity reactions and are the focus of part 2 of this publication series.

resultsType V hypersensitivity is characterized by impairment of epithelial barrier function, resulting in aberrant and persistent activation of the mucosal immune system and, consequently, chronic inflammation. In addition to barrier dysfunction, microbial dysbiosis and dysregulation of immune responses play a major role, including broad activation of Th1, Th2, and Th17 pathways, accompanied by a loss of regulatory T and B cells (Treg, Breg). Further mechanisms involve the production of serum (s)IgE against inhalant or food allergens; activation of macrophages (Mφ); and release of proinflammatory cytokines, chemokines, and inflammatory mediators such as histamine and leukotrienes. Loss of epithelial barrier integrity may result from defects in several key components, including structural elements; tight junction proteins; protective antiproteases; expression of antimicrobial proteins; and altered transport of ions, protons, water, or antimicrobial substances. Disruption of the epithelial barrier is also associated with activation of sensory nerve fibers within the mucosa, thereby contributing to the development of inflammatory symptoms.

conclusionIn patients with CRSwNP, immunological hyperreactivity reactions of various types-particularly type IV, type V, and type VI hypersensitivity-may occur in either isolation or combination. While type IV and type VI reactions primarily contribute to the cellular inflammatory response and chronic persistence, type V reactions, characterized by dysregulated receptor signaling, are increasingly recognized as clinically relevant in the context of epithelial barrier defects and impaired mucosal regeneration. The aim of this second part of the review is to elucidate the mechanisms underlying type V hypersensitivity reactions and to discuss their implications for extended diagnostic and therapeutic approaches in CRSwNP.