https://orcid.org/0000-0002-2933-814X
Key Points
CSF proteomics identified novel CSF biomarkers that can facilitate the diagnosis of CNS-HLH from other neuroinflammatory disorders.
CSF CXCL9 is a promising biomarker for distinguishing CNS-HLH from other neuroinflammatory disorders.
Central nervous system (CNS) hemophagocytic lymphohistiocytosis (HLH) can mimic several other neuroinflammatory disorders (ONID) often leading to misdiagnosis. Current diagnostic studies do not reliably distinguish CNS-HLH from ONID. We hypothesized that novel CSF biomarkers identified using unbiased proteomic analysis can facilitate diagnosis of CNS-HLH from ONID. Banked CSF samples were categorized into 3 groups, CNS-HLH, ONID, and controls without CNS inflammation. Proteomic analysis was performed on 25 samples in each group(total N=75). Proteins with significant changes (>1.5 fold higher and p<0.05) in the CNS-HLH group compared to ONID group and associated with HLH pathological mechanisms were selected as candidate biomarkers. Cross-platform validation of candidate biomarkers and known candidate biomarkers CXCL9 and osteopontin was performed using ELISA analysis. 122 proteins were identified on CSF proteomic analysis at 99% confidence. Of these, 10 proteins showed 1.5-fold change with a p value <0.05 in CNS-HLH vs ONID groups. SerpinG1, Lysozyme, and CD14 were selected as candidate biomarkers. ELISA analysis confirmed significant elevation of all five biomarkers in CNS-HLH compared to ONID. Median SerpinG1 level was 1242.9 ng/ml in CNS-HLH vs 292.2 ng/ml in ONID(p=<0.001). Median lysozyme level was 222.2 ng/ml in CNS-HLH vs 65.6 ng/ml in ONID(p=0.001). Median CD14 level was 180.3 ng/ml in CNS-HLH vs 64.5 ng/ml in ONID(p=<0.001). Median CXCL9 was 223.7 ng/ml in CNS-HLH vs 15.5 ng/ml in ONID(p=<0.001). Median osteopontin was 356.5 ng/ml vs 92.9 ng/ml in ONID(p=0.001). Novel CSF biomarkers SerpinG1, lysozyme and CD14 and CSF CXCL9 can facilitate diagnosis of CNS-HLH from ONID.
