Cellular profiling identifies targetable T cell phenotypes in lymphocytic variant hypereosinophilic syndrome

Lymphocytic variant hypereosinophilic syndrome (LHES) is driven by aberrant Th2_skewed lymphocyte clones that promote tissue eosinophilia. We performed multimodal single_cell RNA_sequencing (scRNA_seq), cell_surface protein (ADT) profiling, and paired alphabeta_TCR sequencing on peripheral_blood mononuclear cells (PBMCs) from two clinically characterized LHES patients and one idiopathic HES control. One LHES patient was sequenced at two timepoints, pre-JAK inhibitor treatment and post-JAK inhibitor treatment. Single_cell regulatory_network inference (SCENIC), CellChat ligand_receptor modelling, and scRNA variant calling were integrated with flow_cytometric validation and 5,000_ amplicon sequencing. Two clonally expanded CD3_CD4_ central_/effector_memory T_cell clusters were observed... (for more see dbGaP study page.)