Komori M, Blake A, Greenwood M, Lin YC, Kosa P, Ghazali D, Winokur P, Natrajan M, Wuest SC, Romm E, Panackal AA, Williamson PR, Wu T, Bielekova B. CSF markers reveal intrathecal inflammation in progressive multiple sclerosis. Ann Neurol. 2015 . doi: 10.1002/ana.24408. [Epub ahead of print]
Objective The management of complex patients with neuroimmunological diseases is hindered by an inability to reliably measure intrathecal inflammation. Currently implemented laboratory tests developed more than 40 years ago are either not dynamic or fail to capture low levels of central nervous system (CNS) inflammation. Therefore, we aimed to identify and validate biomarkers of CNS inflammation in two blinded, prospectively-acquired cohorts of untreated patients with neuroimmunological diseases and embedded controls, with the ultimate goal of developing clinically useful tools.
Methods Because biomarkers with maximum utility reflect immune phenotypes, we included assessment of cell-specificity in purified primary immune cells. Biomarkers were quantified by optimized electrochemiluminescent immuno-assays.
Results Among markers with cell-specific secretion, soluble CD27 is a validated biomarker of intrathecal T cell activation, with an area under the receiver-operating characteristic curve of 0.97. Comparing the quantities of cerebrospinal fluid (CSF) immune cells and their respective cell-specific soluble biomarkers (released by CSF cells as well as their counterparts in CNS tissue) provided invaluable information about stationary CNS immune responses, previously attainable via brain biopsy only. Unexpectedly, progressive and relapsing-remitting multiple sclerosis (MS) patients have comparable numbers of activated intrathecal T and B cells, which are preferentially embedded in CNS tissue in the former group.
We have been saying for some time that progressive MS and RRMS are just parts of a continual spectrum and there is active inflammation going on in progressive MS. This ideally needs to be dealt with just as it needs to dealt with in RRMS. Dealing with the immune response in the Periphery can stop relapsing disease but we also want to stop inflammation in the brain and spinal cord. Most MS drugs are relatively poor at getting into the CNS, and whilst Gilenya easily gets there, its function is to trap the white blood cells in the lymph glands. So a treatment that gets rid of inflammation in the CNS would be useful.