Peripheral Blood ILC2s Levels Are Associated with Autoimmunity and Atopy in Chronic Spontaneous Urticaria: A Preliminary Study

Background: Chronic spontaneous urticaria (CSU) pathogenesis is unclear, with autoimmune and autoallergic mechanisms implicated. Many CSU patients have an atopic background, and group 2 innate lymphoid cells (ILC2s) are involved in atopic and autoimmune diseases, but their role in CSU is unknown. Objectives: This study investigated ILC2s levels in CSU patients, analyzed their correlation with clinical features, and explored ILC2s’ potential role in CSU pathogenesis. Methods: Peripheral blood samples from 68 CSU patients and 53 healthy controls were collected. ILC2s levels in peripheral blood mononuclear cells (PBMCs) were measured using flow cytometry, and correlations with clinical features were analyzed. Results: CSU patients had significantly lower peripheral blood ILC2s levels than healthy controls (p<0.0001). In the CSU group, autologous serum skin test (ASST)-negative patients had higher ILC2s levels than ASST-positive patients (p=0.0053), and atopic CSU patients had higher ILC2s levels than non-atopic CSU patients (p=0.024). However, no significant associations were found between ILC2s levels and disease activity, duration, response to H1-antihistamine therapy, or clinical manifestations like dermographism or angioedema. Conclusion: Reduced peripheral ILC2s levels in CSU may indicate autoimmune dysregulation. While comparaed with non-atopic CSU, the elevated ILC2s in atopic CSU suggest distinct type 2 inflammatory pathways. Yet, ILC2s don’t correlate with clinical severity or treatment response, implying their likely immunomodulatory role in CSU pathogenesis related to autoimmune and atopic mechanisms, not as disease biomarkers. Further research is needed to clarify their exact function and therapeutic potential.