Peripheral blood high-dimension flow cytometry of chronic pruritus of unknown origin reveals il-31 and oncostatin m+ producing circulating blood cd4+ tcells

Summary: Abstract Body: Chronic pruritus of unknown origin (CPUO) is a prevalent yet underrecognized condition that severely impairs quality of life, with no FDA-approved treatments or established clinical guidelines. Characterized by intense, disabling itch without primary skin lesions, CPUO’s pathophysiology remains poorly understood. This study aimed to define circulating blood inflammation in CPUO patients using high-dimensional 17-color flow cytometry of peripheral blood mononuclear cells (PBMCs). PBMCs were analyzed from CPUO patients (n=56; mean age 70 years; 80% Caucasian, 11% African American) and healthy controls (HC, n=21; mean age 51 years; 52% Caucasian, 38% African American). CPUO patients reported a mean Worst-Itch Numeric Rating >8/10. Significantly increased immune cell populations in CPUO patients included CD4+IL31+ T cells (p<0.0125), CD4+OSM+ T cells (p<0.0010), CD8+TNF+ T cells (p<0.0042), γδT+TNF+ cells (p<0.0293), IL6+TNF+ monocytes (p<0.0032), and TNF+ monocytes (p<0.0078). These findings reveal a complex interplay of immune cells and cytokines in CPUO, involving Th1 and Th2 inflammation. Elevated IL-31-producing CD4+ T cells align with Th2-mediated pathways, while increased OSM+ CD4+ T cells suggest a role in neuronal sensitization. TNF-producing cells across multiple lineages emphasize TNF-α’s importance in CPUO pathophysiology. This study provides novel insights into CPUO’s immunological landscape, identifying potential therapeutic targets and biomarkers across T helper cell subsets. These findings may inform future research on targeted therapies to address the unmet need for effective CPUO treatments. Davies Gage¹, Kavita Vats¹, Yagiz M. Akiska¹, Shahin Shahsavari¹, Thomas Pritchard¹, Kevin Lee¹, Louis J. Born¹, Madan M. Kwatra^{2, 3}, Shawn Kwatra¹ 1. Dermatology, University of Maryland Baltimore School of Medicine, Baltimore, MD, United States. 2. Anesthesiology, Duke University School of Medicine, Durham, NC, United States. 3. Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, United States. Translational Studies: Cell and Molecular Biology