Han S, Lin YC, Wu T, Salgado AD, Mexhitaj I, Wuest SC, Romm E, Ohayon J, Goldbach-Mansky R, Vanderver A, Marques A, Toro C, Williamson P, Cortese I, Bielekova B. Comprehensive Immunophenotyping of Cerebrospinal Fluid Cells in Patients with Neuroimmunological Diseases. J Immunol. 2014. [Epub ahead of print]
We performed unbiased, comprehensive immunophenotyping of cerebrospinal fluid (CSF) and blood leukocytes in 221 subjects referred for the diagnostic work-up of neuroimmunological disorders to obtain insight about disease-specific phenotypes of intrathecal immune responses. Quantification of 14 different immune cell subsets, coupled with the assessment of their activation status, revealed physiological differences between intrathecal and systemic immunity, irrespective of final diagnosis. Our data are consistent with a model where the CNS shapes intrathecal immune responses to provide effective protection against persistent viral infections, especially by memory T cells, plasmacytoid dendritic cells, and CD56brightNK cells. Our data also argue that CSF immune cells do not simply reflect cells recruited from the periphery. Instead, they represent a mixture of cells that are recruited from the blood, have been activated intrathecally and leave the CNS after performing effector functions. Diagnosis-specific differences provide mechanistic insight into the disease process in the defined subtypes of multiple sclerosis (MS), neonatal onset multisystem inflammatory disease, and Aicardi-Goutières syndrome. This analysis also determined that secondary-progressive MS patients are immunologically closer to relapsing-remitting patients as compared with patients with primary-progressive MS. Because CSF immunophenotyping captures the biology of the intrathecal inflammatory processes, it has the potential to guide optimal selection of immunomodulatory therapies in individual patients and monitor their efficacy. Our study adds to the increasing number of publications that demonstrate poor correlation between systemic and intrathecal inflammatory biomarkers in patients with neuroimmunological diseases and stresses the importance of studying immune responses directly in the intrathecal compartment.
This study looked at white blood cells from the blood and the spinal fluid of MSers and other inflammatory or non inflammatory neurological diseases and detected twelve immune markers. The first point was not matter what they looked at there was no similarity between the blood and the spinal fluid, so the hundreds of published studies of looking at the blood is not going to provide clues of what is happening the brain. In MSers there were more immune cells (T & B) that in healthy donor and there were more CD4 cells than CD8 although a large number of progressive MSers had low numbers of immune cells, perhaps pointing further to a different mechanism. Whilst there were differences between some MSer subgroups and SPMSers and RRMSers compared to PPMSers in comparison to other neurological controls. There was not much difference between primary and secondary progressive disease with a tendency for RRMsers to have elevated T & B cell response. Have a read.