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

BACKGROUND: The effectiveness of allergen-specific immunotherapy has been proven in studies. Studying the level and expanded spectrum of Th1, Th2, Treg and Breg cytokines against the background of allergen-specific immunotherapy, as well as allergen-specific IgG4 (asIgG4), is promising, which will clarify the mechanisms of the effectiveness of allergen-specific immunotherapy in patients with allergic rhinitis.

AIM: To evaluate the clinical effectiveness of allergen-specific immunotherapy in patients with allergic rhinitis and to identify the most significant biomarkers of the formation of early immunological tolerance.

MATERIALS AND METHODS: We examined 30 patients with allergic rhinitis aged 19 to 60 years who received allergen-specific immunotherapy. The clinical effectiveness was assessed using the validated Combined Symptom Medication Score (CSMS). All patients had their serum levels of IL-4, IL-13, IFN-γ, IL-12, IL-10, TGF-β, and asIgG4 of enzyme-linked immunosorbent assay recorded at baseline and 6 months after the start of allergen-specific immunotherapy.

RESULTS: Allergen-specific immunotherapy has been demonstrated to be highly clinically effective in achieving control of allergic rhinitis. 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-β (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 allergen-specific immunotherapy. We did not register an increase in IFN-γ and the expected increase in IL-10 and decrease of IL-13. The correlation and principal component analysis showed that the clinical effect of allergen-specific immunotherapy was associated with an increase in TGF-β and IL-12, a moderate increase in asIgG4 with a decrease of IL-4.

CONCLUSION: The results demonstrate the high clinical effectiveness of allergen-specific immunotherapy within 6 months from the moment of its initiation. Significant marker of the effectiveness of allergen-specific immunotherapy 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 principal component analysis 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 allergen-specific immunotherapy.