Abstract：
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by prolonged fever, cytopenia, hepatosplenomegaly, and hemophagocytosis. This occurs as a result of activated macrophages and impaired function of natural killer cells and/or cytotoxic T lymphocytes. The NF-κB pathway plays a crucial role in hyperinflammation. Matrin3 (MATR3) is a nuclear RNA/DNA-binding protein that plays multiple roles in the regulation of gene expression. We enroll 62 patients diagnosed with secondary HLH and hemophagocytosis. Peripheral blood (PB) from 25 patients and 30 healthy volunteers and good quality bone marrow (BM) samples from 47 patients are collected and used for analysis. Clinical parameters, including age, sex, etiology, ferritin, fibrinogen, triglyceride, and viral infection status, had no association with survival prediction. Patients with downregulation of NF-κB and MATR3mRNA expression in the BM had a higher mortality rate. MATR3mRNA expression in PB was lower in patients compared to that in healthy volunteers. We use shRNA-MATR3-KD-THP1 cells to determine the efficacy of phagocytosis. We note that shRNA-MATR3-KD-THP1 cells had a higher phagocytic effect on necrotic Jurkat E6 cells and carboxylate modified polystyrene latex beads. Herein, we provide evidence of a new marker for clinical translation that can serve as a potential treatment target for secondary HLH.
摘要：
噬血细胞性淋巴组织细胞增生症（HLH）是一种威胁生命的高炎症综合征，其特征是长时间发烧，血细胞减少,肝脾肿大,和吞噬作用。这是由于活化的巨噬细胞和自然杀伤细胞和/或细胞毒性T淋巴细胞的功能受损而发生的。NF-κB通路在炎症过度中起着至关重要的作用。Matrin3（MATR3）是一种核RNA/DNA结合蛋白，在基因表达调控中起着多种作用。我们招募了62例诊断为继发性HLH和吞噬作用的患者。收集来自25名患者和30名健康志愿者的外周血(PB)和来自47名患者的优质骨髓(BM)样品并用于分析。临床参数,包括年龄,性别,病因学,铁蛋白,纤维蛋白原，甘油三酯，和病毒感染状况，与生存预测无关。BM中NF-κB和MATR3mRNA表达下调的患者死亡率较高。与健康志愿者相比，患者PB中的MATR3mRNA表达较低。我们使用shRNA-MATR3-KD-THP1细胞来确定吞噬作用的功效。我们注意到shRNA-MATR3-KD-THP1细胞对坏死的JurkatE6细胞和羧酸酯修饰的聚苯乙烯乳胶珠具有更高的吞噬作用。在这里，我们提供了一种新的临床翻译标志物的证据,该标志物可作为继发性HLH的潜在治疗靶点.
