Immunomodulatory Effects of Bcg in Patients with Recurrent Respiratory Papillomatosis / Иммуномоделирующие Эффекты Всg У Пациентов С Рецидивирующим Респираторным Папилломатозом

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare manifestation of human papilloma virus (HPV) infection with extremely high relapse frequency, poorly understood immunopathogenesis, and lack of efficient treatment. Immunotherapy with Calgevax (BCG) in combination with CO 2 surgery significantly improves the outcome of RRP. The present study investigates cellular immunity parameters in RRP patients, and the effects of 20-month Calgevax immunomodulation. MATERIALS AND METHODS: RRP patients (n = 15) subjected to combined therapy were tested before, 6, 12 and 20 months after the start of immunomodulation. Absolute counts and percentage of T, B and NK cells, effector Tc1 (CD8 + IFNγ+); Th1 (CD4+IFNγ+), Th17 (CD4+IL-17+) and regulatory (CD4+FoxP3+) T lymphocytes, as well as the in vitro stimulated secretion of IL-2, IL-4, IL-5, IL-10, IFNγ and TNFα were determined by flow cytometry (FACSCanto II, BD). RESULTS: While no significant changes were detected in the circulating T, B and NK subsets, RRP patients presented increased proportions of Tc1, Th1 and Th17 cells, and significantly reduced IFNγ/IL-4 and IFNγ/IL-10 ratios as compared to healthy controls (15% vs. 8%), (58 vs. 139 and 15 vs. 26, respectively), p < 0.05 for all comparisons. Increased Treg (9% vs. 4%), and decreased Th17 effectors share (0.7% vs. 0.4%) were observed at 12 months, while IFNγ/IL-4 and IFNγ/IL-10 ratios were restored after 20 months of Calgevax application. CONCLUSIONS: Antiviral response closely depends on cytokine background. Calgevax potentiates Treg differentiation at the expense of proinflammatory Th17, limits hyperactivation and virus-specific T cell clones depletion, and restores a Th1 cytokine background.