EVALUATION OF THE IMPACT OF GENETICALLY ENGINEERED BIOLOGICAL THERAPY ON HLA-E EXPRESSION IN BRONCHIAL ASTHMA AND ATOPIC DERMATITIS

Abstract

Globally, the prevalence of bronchial asthma alone reaches 19%, with the number of affected individuals showing an upward trend. Atopic dermatitis affects 25-30% of children and 7-10% of adults. Remission remains elusive even with advanced genetically engineered biological therapies. Consequently, research into immunopathogenic pathways and the development of novel therapeutic strategies remain critical. A typical representative of “non-classical” HLAs, the HLA-E molecule, is a perspective for study. These molecules are also expressed across various tissues, notably in the respiratory system (bronchial epithelium) and skin keratinocytes. As a cell surface protein, HLA-E participates in diverse immune response pathways. VL9 peptides stabilize HLA-E expression, enabling presentation to its primary receptors, NKG2, on natural killer (NK) cells. In adaptive immunity, HLA-E serves as a ligand for CD8+ cytotoxic T-cell receptors (TCRs). This study aimed to evaluate HLA-E-bearing cells (CD4+, CD8+, CD14+) in patients with bronchial asthma (BA) and atopic dermatitis (AD), both before and 12 months after initiating genetically engineered biological therapy (GEBT). Peripheral blood mononuclear cells (PBMCs) were analyzed from healthy donors (n=16), BA patients (n=4), and AD patients (n=5). AD patients received dupilumab (300 mg loading dose), while BA patients were treated with benralizumab (30 mg). Prior to therapy, both AD and BA patients exhibited lower proportions of HLA-E-positive CD4+ and CD8+ T-cells compared to healthy donors. No significant differences were observed in HLA-E expression on CD14+ monocytes. During treatment, HLA-E levels across all cell types in patients reached levels comparable to those in healthy donors. These findings suggest HLA-E’s involvement in disease pathogenesis and the modulating effects of GEBT on HLA-E-positive cell populations.