Expression and clinical significance of Toll-like receptor 4 on peripheral blood CD14 + monocytes of patients with secondary haemophagocytic lymphohistiocytosis

Abstract

Abstract Background Secondary haemophagocytic lymphohistiocytosis (sHLH) develops predominantly in adulthood and is triggered by a number of factors, with a lack of reliable immune biomarkers for predicting aetiology. Toll-like receptor 4 (TLR4), an evolutionarily conserved regulator of innate and adaptive immune responses, may be involved in hyperinflammation in sHLH. Methods This study retrospectively included 20 newly diagnosed adult sHLH patients diagnosed from July 2019 to December 2020. To investigate TLR4 expression and clinical significance in sHLH, we recruited 20 newly diagnosed sHLH patients and 10 healthy controls and evaluated TLR4 expression on peripheral blood CD14+ monocytes by flow cytometry. Results TLR4 levels were significantly elevated in the sHLH group compared with the healthy control group (P = 0.001). Specifically, TLR4 was expressed on greater than 5% of CD14+ cells, up to 65%. Determination of TLR4 levels in the infection-associated HLH (IHLH) group showed a remarkable increase compared with those in the lymphoma-associated HLH (LHLH) group (P = 0.001). No significant difference was found in expression of TLR4 on CD14+ monocytes between the infection-associated HLH (IHLH) group and the autoimmune-associated HLH (AHLH) group (P = 0.066) or between the AHLH group and the LHLH group (P = 0.5). Expression of CD14+/TLR4+ monocytes in patients with clinical remission was significantly lower than the pretreatment level (P = 0.04). Conclusions These results support testing of TLR4 expression on CD14+ monocytes, which may contribute to IHLH diagnosis and development surveillance.