Peripheral blood dendritic cell subtype alterations in polycythemia vera: Clinical correlations with disease risk and inflammatory profile

Abstract Background: Polycythemia vera (PV) is characterized by chronic inflammation and immune dysfunction, yet the role of dendritic cells (DCs) remains poorly understood. DCs are critical antigen-presenting cells that bridge innate and adaptive immunity, with distinct functional subtypes including conventional DC1 (cDC1), conventional DC2 (cDC2), and plasmacytoid DC (pDC). Emerging evidence suggests DC dysfunction may contribute to myeloproliferative neoplasm pathogenesis through altered immune surveillance and inflammatory signaling. Understanding DC subtype alterations in PV may provide insights into disease mechanisms and potential therapeutic targets. Methods: We analyzed 112 PV patients diagnosed according to WHO 2016 criteria and 30 age-matched healthy controls. Peripheral blood DC subtypes (cDC1, cDC2, pDC) were quantified by multiparameter flow cytometry. Symptom burden was assessed using validated instruments: MPN-10, MD Anderson Symptom Inventory (MDASI), and EORTC QLQ-C30. Serum interleukin (IL)-6, IL-8, and IL-10 levels were measured by enzyme-linked immunosorbent assay. Statistical analyses included receiver operating characteristic (ROC) curves, correlation analysis, and comparison across risk groups stratified by established criteria. Results: PV patients demonstrated significant reductions in total DC and cDC1 absolute counts compared to controls (both p<0.001), while pDC and cDC2 counts remained unchanged. ROC analysis identified cDC1 absolute count ≤0.017×10⁹/L as optimal discriminatory threshold (AUC=0.729, specificity=90%). High-risk PV patients exhibited significantly lower cDC2 levels versus low-risk patients (p=0.003). Patients with splenomegaly showed reduced cDC1 counts compared to those without splenomegaly (p=0.023). Inflammatory cytokine profiling revealed significantly elevated IL-6, IL-8, and IL-10 in PV patients versus controls (all p<0.001). Despite these immunological alterations, DC levels showed no correlation with patient-reported symptom burden across all validated questionnaires. Conclusions: This study reveals profound alterations in peripheral DC homeostasis in PV, with selective cDC1 depletion representing a novel biomarker with high diagnostic specificity. The differential impact on DC subtypes—with preserved pDC but reduced cDC1—suggests specific disruption of antigen presentation pathways potentially contributing to immune evasion. The association between DC depletion and disease risk stratification, combined with elevated inflammatory cytokines, supports a model where DC dysfunction facilitates disease progression through compromised immune surveillance. Notably, the absence of correlation between DC levels and symptom burden suggests that immune dysregulation may precede or operate independently of clinical symptoms in PV. These findings establish DC profiling as a potential diagnostic tool and support further investigation into DC-targeted approaches in PV management.