Plasma citrulline levels are increased in patients with multiple sclerosis

Background: Multiple sclerosis is an inflammatory demyelinating disorder of the central nervous system (CNS). Myelin basic protein (MBP), which is one of the main compounds of CNS myelin, appears to be hypercitrullinated in the brain of patients with MS. We hypothesized that MS is associated with an increased release of citrulline from the brain.Methods: Twenty-five patients with MS, 25 controls without neurological disease (CwND) and 25 subjects with non-MS cerebral white matter lesions were included in this study. Groups were matched for age and gender. Clinical MS disability measures were recorded by means of Expanded Disability Status Scale (EDSS) scores and Multiple Sclerosis Severity Scores (MSSS). Citrulline was assessed in plasma obtained from an antecubital peripheral vein (PV) in all participants. Additional internal jugular vein (IJV) samples were examined in 10 patients with MS and 10 CwND. Twelve patients with MS underwent brain magnetic resonance imaging to determine total brain and T2 fluid-attenuated inversion recovery lesion volume.Results: Median [IQR] PV citrulline levels were increased in patients with MS (50.47 [86.61] pM), as compared to CwND (33.58 [43.65] pM, P = 0.042) and subjects with non-MS cerebral white matter lesions (32.41 [28.86] pM, P = 0.006). Citrulline IJV levels and IJV/PV ratios were comparable between patients with MS and CwND. No significant correlations were found between PV citrulline levels and any of the clinical, nor radiological, disease measures.Conclusion: PV plasma levels of citrulline are elevated in patients with MS but this does not seem to result from an augmented release from the brain. Increased plasma citrulline may be a promising new biomarker in MS but the origin and significance need to be further elucidated.