Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

CD163+ monocytes and soluble CD163 as prognostic indicators in severe fever with thrombocytopenia syndrome: An integrative analysis.

Abstract

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) carries high short-term mortality and lacks approved antiviral therapy, highlighting the need for admission risk tools grounded in upstream host immune pathobiology. METHODS: Public single-cell RNA sequencing (scRNA-seq) data (GSE175499) from 15 SFTS patients (4 non-survivors, 11 survivors) and 4 healthy controls were reanalyzed to map cell-cell communication and identify monocyte subsets and pathways. Findings were validated by bulk RNA sequencing and flow cytometry. A multicenter clinical cohort (n = 150, 132 survivors and 18 non-survivors) measured admission sCD163 using enzyme-linked immunosorbent assay (ELISA) and assessed 30-day mortality using area under the curve (AUC), Kaplan-Meier, and Cox models. RESULTS: Single-cell analysis identified expansion of CD163 + intermediate monocytes in SFTS, along with antiviral and complement activation programs in non-survivors. Communication analysis prioritized thrombospondin (THBS) signaling with the dominant sender shifting from CD163 + intermediate (survivors) to CD163 + classical monocytes (non-survivors). Flow cytometry confirmed increased CD163 + monocytes in SFTS. At admission, sCD163 independently predicted 30-day mortality (optimal threshold = 1.17 microg/mL, AUC 0.80). A two-marker model combining sCD163 with blood urea nitrogen (BUN) improved discrimination (AUC 0.87), yielded stepwise separation across three risk tiers (Score 0, 1, and 2) and replicated externally (AUC 0.73 and 0.83). Elevated sCD163 was consistently associated with higher mortality across sex and age subgroups. However, further subgroup analyses within the three-tier risk score were limited by small sample sizes and should be considered exploratory. CONCLUSIONS: We identified and orthogonally validated CD163 + monocyte programs linked to outcomes, establishing admission serum sCD163 as a biomarker. An admission two-marker score (sCD163 and BUN) provides a simple three-tier admission score that rapidly stratifies 30-day mortality risk and guides intensified monitoring and timely supportive care.