Identifying novel CSF Biomarkers for the Diagnosis of Isolated CNS Hemophagocytic Lymphohistiocytosis
Dr. Sharat Chandra
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio USA
Date of Award
Amount of Award
Primary Hemophagocytic Lymphohistiocytosis (HLH) is an inherited syndrome of excessive inflammation. While involvement of the brain i.e., CNS-HLH is common in primary HLH, a proportion of patients with primary HLH can present with CNS-HLH without any systemic signs and symptoms (i.e., isolated CNS-HLH). However, this clinical presentation can mimic several other disorders that are associated with inflammation in the brain. Patients often get diagnosed with a non-HLH disorder of brain inflammation leading to a delay in diagnosis of isolated CNS-HLH, which is usually confirmed when genetic testing identifies mutations in genes known to be associated with HLH. Current CSF diagnostic studies for CNS-HLH do not reliably distinguish isolated CNS-HLH from other non-HLH disorders of inflammation.
Elevated CSF protein, white cells seen in CNS-HLH can also be seen in other disorders. Delay in diagnosis of isolated CNS-HLH leads to inappropriate therapy that can lead to poor neurological outcomes from ongoing injury to the brain. There is therefore a compelling need for novel CSF biomarkers of CNS-HLH that facilitate prompt diagnosis and appropriate early intervention in isolated CNS-HLH. Global protein profiling by mass spectrometry (MS)-based proteomicshas evolved to optimally unravel new candidate protein biomarkers involved in different diseases, including neurodegenerative disorders. The sensitivity, speed, and the practicability of the different proteomics approaches has improved rapidly over the years, leading to the discovery of an enormous number of biomarker candidates.
We propose that novel CSF biomarkers identified by proteomic analysis can reliably distinguish isolated CNS-HLH from other disorders of brain inflammation. By facilitating diagnosis and appropriate early treatment of isolated CNS-HLH, these novel biomarkers can potentially improve outcomes for patients with isolated CNS-HLH, particularly neurological outcomes. Identified novel biomarkers may also have a role in monitoring response to treatment, further helping management of patients with HLH.