Features of the formation of early immunological tolerance during immunotherapy with allergens in patients with allergic rhinitis.

Background: The effectiveness of AIT has been proven in studies. Studying the level and expanded spectrum of Th1, Th2, Treg and Breg cytokines against the background of AIT, as well as asIgG4, is promising, which will clarify the mechanisms of the effectiveness of AIT in patients with AR. Aim: To evaluate the clinical effectiveness of AIT in patients with AR and to identify the most significant biomarkers of the formation of early immunological tolerance. Materials and methods We examined 30 patients with AR aged 19 to 60 years who received AIT. The clinical effectiveness was assessed using the CSMS. All patients had their serum levels of IL-4, IL-13, IFN-γ, IL-12, IL-10, TGF-β, and asIgG4 recorded at baseline and 6 months after the start of AIT. Results: AIT has been demonstrated to be highly clinically effective in achieving control of AR. At baseline, the total CSMS score was 3.75 [3.33; 4.5], at the end of 6 months - 1.83[1.17;2.67] (p=0.000002). When analyzing the dynamics of the cytokine profile and asIgG4, an increasing in the level of TGF-b (p = 0.000002), IL-12 (p = 0.000002) and asIgG4 (p = 0.000003) was revealed, as well as a decreasing in the level of IL- 4 (p=0.000024) 6 months after the start of AIT. We did not register an increase in IFN-γ and the expected increase in IL-10 and decrease of IL-13. The correlation and PCA showed that the clinical effect of AIT was associated with an increase in TGF-β and IL-12, a moderate increase in asIgG4 with a decrease of IL-4. Conclusions: The results demonstrate the high clinical effectiveness of AIT within 6 months from the moment of its initiation. Significant marker of the effectiveness of AIT at the stage of early tolerance formation is TGF-β, which increasement was in correlation with an increased IL-12 with a decrease of IL-4. The increase in asIgG4 is less pronounced. The conducted correlation and PCA showed the relationship of the discussed biomarkers with the CSMS, which may indicate in favor of their choice as potential biomarkers for assessing the effectiveness of AIT.