Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Potential role and mechanism for high mobility group box1 in childhood chronic immune thrombocytopenia.

Abstract

OBJECTIVE: High mobility group box1(HMGB1) can be used as PAMP or alarmins to stimulate the innate immune system; however, previous research on immune thrombocytopenic purpura (ITP) mainly focused on its adaptive immunity. The study aimed to determine whether HMGB1 is associated with chronic ITP (cITP) during childhood and investigate its role in innate immunity in childhood cITP. PATIENTS AND METHODS: We recruited 80 patients to measure the expression of HMGB1, IL-17, and IL-10; 55 patients were recruited to measure the expression of TLR2 and TLR4 in monocyte and CD1c+dendritic cells, and 30 volunteers were included as controls. We focused on the expression of the NLRP3 inflammasome during childhood cITP. Furthermore, the impact of HMGB1 on the NLRP3 inflammasome was explored. RESULTS: The expressions of HMGB1 and IL-17 increased in children with cITP, while that of IL-10 decreased; HMGB1 was correlated with the expression of IL-17 and IL-10. The expression of TLR2 in CD14++CD16+, CD14+CD16++ monocytes increased significantly in comparison with the controls; the contrary was observed regarding TLR4. The expression of NLRP3, IL-1β, and IL-18 was significantly higher in CD14 and CD1c, respectively. As the concentration of HMGB1 increased, the expression of NLRP3, IL-1β, and IL-18 increased in different degrees. CONCLUSIONS: HMGB1 could be used as an early warning alarm for childhood cITP and is involved in developing cITP. HMGB1 could affect the incidence and development of chronic childhood ITP via the NLRP3, TLR2/TLR4 pathways.