Yoshiki Kawamura

ABSTRACT Human herpesvirus 6B (HHV‐6B) encephalitis is a rare but severe complication of hematopoietic cell transplantation. This study investigated the pathogenesis of HHV‐6B encephalitis by comparing plasma proteomic profiles of four pediatric patients with HHV‐6B encephalitis to three with asymptomatic HHV‐6B reactivation following umbilical cord blood transplantation (UCBT). Plasma proteomic profiling was conducted using liquid chromatography‐mass spectrometry. Overall, 260 proteins were identified and quantified in plasma samples. At the onset of HHV‐6B encephalitis and asymptomatic reactivation, 20 and 24 proteins, respectively, were significantly upregulated compared to their respective pre‐onset levels. Of these, 11 proteins were uniquely upregulated in HHV‐6B encephalitis. S100‐A9 and S100‐A8 were the most and second‐most upregulated proteins in HHV‐6B encephalitis, respectively. Elevated plasma S100A8/A9 heterodimer levels were confirmed via enzyme‐linked immunosorbent assay in three of the four patients with HHV‐6B encephalitis. Pathway analysis identified neutrophil degranulation as the most enriched category among upregulated proteins in HHV‐6B encephalitis. Additionally, proteins related to the protein‐lipid complex remodeling pathway were more prominently upregulated in HHV‐6B encephalitis than in asymptomatic reactivation. Proteomic analysis revealed distinct plasma protein profiles between HHV‐6B encephalitis and asymptomatic HHV‐6B reactivation in pediatric UCBT recipients. The inflammatory response mediated by S100A8/A9 proteins may play a critical role in the pathogenesis of HHV‐6B encephalitis. These findings indicate that proteomic analysis may provide novel insights into the host response to HHV‐6B reactivation and the subsequent development of HHV‐6B encephalitis.