The value of C‐X‐C motif chemokine ligand 9 ( <scp>CXCL9</scp> ) in the differential diagnosis and management of haemophagocytic lymphohistiocytosis

To identify key cytokines for the differentiation and treatment monitoring of haemophagocytic lymphohistiocytosis (HLH). We retrospectively analysed the clinical data and cytokine profiles from 66 patients with HLH, sepsis, Kawasaki disease (KD) and infectious mononucleosis (IM). Hierarchical clustering analysis was performed among those diseases. The diagnostic value of the markers was assessed using logistic regression and receiver operating characteristic (ROC) curves. Longitudinal changes in cytokines were detected in HLH patients. Cluster analysis revealed substantial overlap in the cytokine profiles between HLH and IM, characterized by high levels of C-X-C motif chemokine ligand 9 (CXCL9), C-X-C motif chemokine ligand 10 (CXCL10), interferon-gamma (IFN-γ), soluble cluster of differentiation 25 (sCD25) and interleukin-18 (IL-18). The cytokine profiles differed from sepsis and KD patients. The combined detection of CXCL9 and haemoglobin (Hb) achieved an area under the curve (AUC) of 0.943 for distinguishing Epstein-Barr virus-related HLH (EBV-HLH) from IM. CXCL9 was significantly correlated with aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in HLH patients. Moreover, high levels of CXCL9 were associated with more severe clinical manifestations. During the monitoring of HLH cases, trends in CXCL9 and LDH levels correlated with disease progression.In conclusion, differences in cytokine profiles contribute to disease differentiation, and detection of CXCL9 holds promise for HLH diagnosis and longitudinal monitoring.