Cerebrospinal Fluid IL-12p40 Is a Biomarker of Intrathecal Inflammation in Multiple Sclerosis (S40.006)

Abstract

Objective: To evaluate the utility of cerebrospinal fluid (CSF) IL-12p40 as a biomarker of MS disease activity and to compare it with CSF CXCL13 and IL-8, two biomarkers of intrathecal inflammation previously linked to MS. Background Biomarkers of intrathecal inflammation could improve diagnosis and understanding of the pathophysiology of neuroimmunological disorders, including multiple sclerosis (MS). Design/Methods: IL-12p40, CXCL13 and IL-8 concentrations were determined in the CSF samples obtained in a pilot cohort (n=72) and a confirmatory cohort (n=167) of untreated patients who presented for diagnostic work-up of a possible neuroimmunological disorder. Correlations were determined with contrast enhancing lesions (CEL) and receiver operating characteristic (ROC) curve analysis in conjunction with principal component analysis (PCA) was used to assess the diagnostic value of CSF biomarkers. Results: All three CSF biomarkers were significantly increased in MS or other inflammatory neurological diseases (OIND) in comparison to non-inflammatory neurological disorder patients (NIND) at least in one cohort. IL-12p40 was overall the strongest and most consistent predictor of intrathecal inflammation, resulting in fair to excellent clinical accuracy (age-adjusted Area under the curve (AUC) value of 0.791-0.904). Considering all three biomarkers in PCA analysis improved ROC curve analysis to consistently good to excellent range (AUC = 0.852-0.924). Conclusions: CSF IL-12p40 measured in conjunction with CXCL13 and IL-8 may provide clinical utility in determining presence of active intrathecal inflammatory process in diagnostically uncertain cases and in therapeutic development and management. Supported by: The intramural research program of the NINDS/NIH. Disclosure: Dr. Herman has nothing to disclose. Dr. Wu has nothing to disclose. Dr. Bielekova has received royalty payments from NIH.