GSDMD and p-MLKL elevated earlier and higher in M1-captured leukocytes for early detection of bloodstream infection in patients with hematopoietic stem cell transplantation.

Bloodstream infections (BSIs) pose a serious threat to patients undergoing hematopoietic stem cell transplantation (HSCT). However, the low abundance of routine infection markers-including procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6)-limits their diagnostic utility for early detection. Identifying markers that rise earlier than conventional indicators remains a pressing challenge. We previously prepared a recombinant mannan-binding lectin (MBL) termed M1 and found that magnetic beads coated with M1 (M1-beads) primarily enriched abnormal leukocytes from the blood of HSCT patients with BSI within 3 h of fever onset. Compared with leukocytes from normal controls, these M1-captured cells exhibited more pronounced features of PANoptosis, including higher expression levels of gasdermin D (GSDMD), phosphorylated mixed lineage kinase domain-like protein (p-MLKL), and interleukin-18 (IL-18); more evident double staining with Annexin V-FITC/propidium iodide (PI); and more distinct morphological characteristics of PANoptosis under transmission electron microscopy (TEM). At this early time point, however, routine plasma infection markers (PCT, CRP, and IL-6) remained not significantly elevated in BSI patients. Collectively, these findings demonstrated that GSDMD and p-MLKL rose earlier and reached higher levels in M1-captured PANoptotic leukocytes, highlighting their potential as early host-derived biomarkers for the adjunctive diagnosis of BSI in HSCT patients.