Comparison of plasma proteomic profiles of patients with Epstein‐Barr virus‐associated hemophagocytic lymphohistiocytosis and infectious mononucleosis

Primary Epstein‐Barr virus (EBV) infection occasionally causes EBV‐infectious mononucleosis (EBV‐IM) and EBV‐hemophagocytic lymphohistiocytosis (EBV‐HLH). Although EBV‐IM is mostly mild and self‐limiting, EBV‐HLH is a life‐threatening disease characterized by excessive immune activation. However, the pathogenesis of EBV‐HLH is yet to be fully elucidated. A diagnostic biomarker for EBV‐HLH is desirable because early diagnosis and treatment are critical for the effective management of patients. In this study, the proteomic profiling of plasma was performed using liquid chromatography‐mass spectrometry to identify proteins specific to EBV‐IM and EBV‐HLH. Furthermore, pathway analysis was performed for the proteins upregulated in patients with EBV‐IM and EBV‐HLH. Compared to healthy controls, 63 and 18 proteins were upregulated in patients with EBV‐IM and EBV‐HLH, respectively. Pathway and process enrichment analyses revealed that the complement system was the most enriched category of upregulated proteins in EBV‐IM, whereas proteins related to immune effector processes were the most enriched in EBV‐HLH. Among the 18 proteins upregulated in EBV‐HLH, seven were exclusive to EBV‐HLH. These specific proteins were associated with three pathways, and apolipoprotein E was commonly found in all the pathways. Proteomic analysis may provide new insights into the host response to EBV infection and the pathogenesis of EBV‐related diseases.