Thursday, 25 August 2016

Clonal Expansions in MS Society

de Paula Alves Sousa A, Johnson KR, Nicholas R, Darko S, Price DA, Douek DC, Jacobson S, Muraro PA.Intrathecal T-cell clonal expansions in patients with multiple sclerosis.Ann Clin Transl Neurol. 2016 Apr 20;3(6):422-33.

OBJECTIVE:Analysis of the T-cell receptor (TCR) repertoire in the cerebrospinal fluid (CSF) of patients withmultiple sclerosis (MS) can reveal antigen-specific immune responses potentially implicated in the disease process. We applied a new unbiased deep-sequencing method for TCR repertoire analysis to accurately measure and compare receptor diversity and clonal expansions within the peripheral and CSF-trafficking T-cell populations of patients with MS and control individuals with idiopathic intracranial hypertension (IIH).
METHODS:Paired blood and CSF TCR β-chain libraries from five MS patients and five IIH controls were sequenced, yielding a total of 80 million reads.
RESULTS:Although TCR repertoire diversity was greater in the blood and CSF compartments of MS patients when compared with IIH controls, it is notable that the frequency of clonal expansions was also significantly higher in both compartments of MS patients. Highly expanded T-cell clones were enriched in the CSF compartment of MS patients compared to peripheral blood, very few of them were detected in both compartments.
INTERPRETATION:Collectively, our data provide a proof of principle that private compartmentalized T-cell expansion exists in the intrathecal space of MS patients.
The target detecting molecules of a T cell is called the T cell receptor. If MS is autoimmune you would think that the disease causing cell would be expanded from the initial naive cell to the effector cell causing the disease.  By sequencing the T cell receptor you can work out if two cells are clonal i.e. are the same because they come from the same originating cell. In this study they looked at the T cell receptor sequences and found that in MS there were evidence of expansions and there were expansions in the CNS, but are these the autoimmune? 

This the next challenge is to work out what they are binding to 

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