HMGB1 is increased in patients with immune thrombocytopenia and negatively associates with Tregs

• Published in: Thrombosis research 2022-05, Vol.213, p.128-136
• Main Authors: Zhang, Guoyang, Yang, Pengfeng, Liu, Xiaoyan, Liu, Hongyun, Wang, Jue, Wang, Jieyu, Xiao, Jie, Nie, Danian, Ma, Liping
• Format: Article
• Language: English
• Subjects: Adult; Forkhead Transcription Factors - metabolism; High mobility group box B1 (HMGB1); HMGB1 Protein - metabolism; Humans; Immune thrombocytopenia (ITP); Interleukin-10; Interleukin-17 - metabolism; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Purpura, Thrombocytopenic, Idiopathic - genetics; Quality of Life; Regulatory T cells (Treg); Splenectomy; T helper 17 cells (Th17); T-Lymphocytes, Regulatory
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2022.02.021

Refractory or recurrent immune thrombocytopenia (ITP) patients suffer from the dual threat of high mortality and drug toxicity in addition to a very poor quality of life. Previous studies have shown that high mobility group box 1 (HMGB1) can promote the development of rheumatoid arthritis, systemic lupus erythematosus, and other autoimmune diseases. However, there is still a lack of research on the role of HMGB1 in the pathogenesis of ITP and whether it can be used as a predictor of efficacy and prognosis. 20 patients of adult ITP with splenectomy were chosen as the experimental group, while 19 adults underwent splenectomy for traumatic splenic rupture without other diseases as the control group. We measured the expression of HMGB1, RORγt and Foxp3 in spleen tissues by immunohistochemistry. Another 50 patients, of which 20 were newly diagnosed without treatment and 30 were refractory ITP, and 25 healthy controls were enrolled to analyse the expression levels and mRNA levels of HMGB1, RORγt and Foxp3 in peripheral blood by Western blot and RT-qPCR. The expression of HMGB1, IL-17 and IL-10 in serum was assayed by ELISA. PBMCs from newly diagnosed ITP patients were cultured in vitro which stimulated with recombinant humanHMGB1 (rHMGB1) and its inhibitors, in which the expressions of RORγt and Foxp3 were measured. The expression of HMGB1 in the spleen with refractory ITP was significantly higher, while Foxp3 was decreased. A significant negative correlation was found between HMGB1 and Foxp3, and the overexpression of HMGB1 was significantly correlated with poor efficacy after splenectomy. The expression of HMGB1 and IL-17 increased and showed a positive correlation in serum, while IL-10 decreased and was negatively correlated with HMGB1. In PBMCs, the expression of HMGB1 and RORγt increased, while Foxp3 decreased, and the differences were more obvious in the refractory chronic ITP group. In a coculture system with PBMCs of untreated ITP patients, rHMGB1 increased RORγt expression and decreased Foxp3 expression, while an antiHMGB1 antibody partially corrected the above changes. Our results suggest that HMGB1 is associated with the imbalance of Treg/Th17 cells and is involved in the pathogenesis of ITP.