Inflammatory Cytokines, Inflammasome, and Neutrophil Extracellular Traps in Primary Immune Thrombocytopenia Pathogenesis Open Access

Immune dysregulation, inflammatory cytokines, and the NLRP3 inflammasome have a central role in the pathophysiology of ITP.

The evidence supports the Th17 pathways and NLRP3 inflammasome as key drivers of inflammation in primary ITP, with IL-18 and IL-17 linked to disease activity.

The NLRP3 inflammasome expression and activity was notably increased within the primary immune thrombocytopenia population/subgroups.

Primary immune thrombocytopenia (ITP) is a disorder characterized by enhanced platelet clearance and impaired production due to immune dysregulation. Central to its pathogenesis are platelet autoantibodies, T-cell-mediated processes, and altered cytokine profiles, which collectively exacerbate clearance and hinder production. These mechanisms mirror other immune-mediated diseases and contribute to symptoms like fatigue and thromboembolism. Despite extensive research, the inflammatory role in ITP remains unclear, with variability across studies underscoring the need for further investigation to optimize therapies. This study aims to summarize the evidence on inflammatory cytokines, inflammasomes, and neutrophil extracellular traps (NETs) in adult primary ITP. A systematic literature review was conducted using Embase and MEDLINE® (search date: January 9, 2024), covering publications from the past decade. Observational studies and clinical trials reporting inflammatory markers were included (79 studies). Most studies were case-control (69.7%) and conducted in China (77.2%). Activation of multiple immune and inflammatory pathways in adult primary ITP was observed. Th17 (n=21) and Tfh cells (n=4) demonstrated involvement, with Th17-derived IL-17 contributing prominently to the inflammatory milieu. NLRP3 inflammasome hyperactivity/increased expression (n=6 studies) emerged as a significant pathway, and strongly associated markers (IL-18 [n=4]) were elevated in active ITP. Additionally, NETs and neutrophil activation promoted inflammation and thrombosis in ITP (n=2). In conclusion, immune dysregulation from Th17 cell pathways and NLRP3 inflammasome strongly contribute to inflammation in adults with primary ITP, with IL-18 and IL-17 linked to disease activity/progression. The findings suggest a need for novel therapies to target immune dysregulation and clarify their roles in ITP manifestations.