Genes and cells associated with sublingual allergen immunotherapy revealed by integrated transcriptome analysis in allergic rhinitis patients.

Background: Sublingual allergen immunotherapy (SLIT) is known as an effective therapy for allergic rhinitis (AR), although its efficacy varies across different treatment duration and individuals. The factors associated with the duration and response of SLIT need to be explored. Methods: Twenty-seven AR patients undergoing SLIT and three healthy volunteers were recruited. Peripheral blood mononuclear cells were isolated for RNA sequencing, and key results were further examined by quantitative PCR (qPCR) in available PBMC samples. Time-correlated and response-associated genes were identified and analyzed using bioinformatic tools. The data were further integrated with single-cell transcriptome. Results: We first identified 164 genes significantly correlated with SLIT duration. The expressions of genes associated with immunoregulation, nitric oxide and serotonin transportation were regulated as the treatment proceeded. qPCR validation further showed a significant positive correlation between SLC6A4 expression and SLIT duration, while SH2D1B and ARG1 showed positive trends. Then, we identified 257 up-regulated and 349 down-regulated genes in SLIT responders. Several pathways were enriched in these genes, including interferon signaling (up-regulated in responders) and granulocytes migration (down-regulated in responders). Single-cell and deconvolution analyses suggested that natural killer cell-associated signals may associate with SLIT efficacy, potentially in relation to T-cell-regulatory and eosinophil-migration-related transcriptional programs. Conclusions: This study revealed potential genes and cells associated with SLIT duration and response. Regulation of T cells and NK cells may play a crucial role in the successful treatment responses. Further studies are required to validate these findings and assess their clinical relevance.