Cytokine signatures in immune thrombocytopenia across clinical stages

Abstract

Abstract Immune Thrombocytopenia (ITP) is an autoimmune disorder marked by decreased platelet counts due to accelerated destruction and/or insufficient production, leading to variable bleeding manifestations. Its clinical heterogeneity, spanning acute, chronic, and refractory phases, requires a deeper understanding of underlying immunological mechanisms. T-cell dysregulation and impaired regulatory T cell (Treg) functions are central to ITP's pathophysiology. Cytokines, critical mediators of immune cell signaling, significantly contribute to the inflammatory response driving disease progression. Elevated pro-inflammatory cytokines (e.g., IL-6, TNF-α) and dysregulated anti-inflammatory responses, including altered IL-10 production, may reflect or influence disease activity. This study aimed to characterize and compare pro-inflammatory and anti-inflammatory cytokine profiles in 17 patients, classified into five groups: Healthy Controls (n=5), Chronic Controlled with Treatment (CCT, n=3), Chronic Controlled without Treatment (CST, n=2), Chronic Uncontrolled with Treatment (NCCT, n=5), and Chronic Uncontrolled without Treatment (NCST, n=2). Platelet counts validated group stratification (CCT: 291.0 ± 115.37 x 10^3/mL; NCCT: 59.0 ± 43.19 x 10^3/mL; CST: 193.0 ± 26.87 x 10^3/mL). Our analysis revealed complex cytokine patterns. IL-17A (61.35 ± 3.61 pg/mL in CCT) showed unexpected levels, not inversely correlating with platelet counts. IL-6 was notably elevated in CST (32.20 ± 2.32 pg/mL) and NCST (30.16 ± 7.98 pg/mL), suggesting a complex role in remission and uncontrolled disease. IL-10 was consistently elevated in CST (16.06 ± 0.14 pg/mL) and NCST (15.96 ± 1.64 pg/mL), indicating a context-dependent regulatory or compensatory role. Conversely, IFN-γ, TNF-α, IL-4, and IL-2 showed minimal variation, limiting their utility as systemic biomarkers. These findings highlight unique cytokine signatures, particularly for IL-6 and IL-10 in patients with treatment-free remission.