Single-cell profiling reveals novel cellular heterogeneity of monocytes during Hymenoptera venom allergy.

Background: Hymenoptera stings can induce dysregulated inflammation and immediate hypersensitivity reactions including anaphylaxis. However, the molecular mechanisms underlying peripheral immune responses during Hymenoptera venom allergy (HVA) remain elusive. Methods: Here we determined the single-cell transcriptomic profiling from highly heterogeneous peripheral blood cells in patients with HVA through unbiased single-cell RNA sequencing and multiple models of computational analyses. Results: Through clustering analysis by uniform manifold approximation and projection, we revealed an increased number of monocytes in the acute phase and identified innate immune responses, leukocyte activation, and cellular detoxification as the main involved biological processes. We used filter analysis to identify that CLU that encodes clusterin was highly expressed in monocytes, and the co-expressed genes of CLU further supported the key role of monocyte. We further used pseudo-temporal ordering of cells and scRNA velocity analysis to delineate disease-associated monocyte lineages and states in patients with HVA. Conclusions: Our comprehensive molecular profiling of blood samples from patients with HVA revealed previously unknown molecular changes, providing important insights into the mechanism of venom allergy and potential therapeutic targets.