The soluble form of Toll-like receptor 2 is elevated in serum of multiple sclerosis patients: a novel potential disease biomarker

Hossain, Jakir and Morandi, Elena and Tanasescu, Radu and Frakich, Nanci and Caldano, Marzia and Onion, David and Faraj, Tola A. and Erridge, Clett and Gran, Bruno (2018) The soluble form of Toll-like receptor 2 is elevated in serum of multiple sclerosis patients: a novel potential disease biomarker. Frontiers in Immunology, 9:457. ISSN 1664-3224

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Official URL: http://dx.doi.org/10.3389/fimmu.2018.00457

Abstract

Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. It was previously shown that Toll-like receptor (TLR)-2 signalling plays a key role in the murine experimental autoimmune encephalomyelitis (EAE) model of MS, and that TLR2-stimulation of regulatory T cells (Tregs) promotes their conversion to T helper 17 (Th17) cells. Here, we sought potential sources of TLR2 stimulation and evidence of TLR2 activity in MS patient clinical samples. Soluble TLR2 (sTLR2) was found to be significantly elevated in sera of MS patients (n=21), in both relapse and remission, compared to healthy controls (HC) (n=24). This was not associated with the acute phase reaction (APR) as measured by serum C-reactive protein (CRP) level, which was similarly increased in MS patients compared to controls. An independent validation cohort from a different ethnic background showed a similar upward trend in mean sTLR2 values in relapsing-remitting MS (RRMS) patients, and significant differences in sTLR2 values between patients and healthy controls were preserved when the data from the two cohorts were pooled together (n=41 RRMS and 44 HC, P=0.0006). TLR2-stimulants, measured using a human embryonic kidney (HEK-293) cell transfectant reporter assay, were significantly higher in urine of MS patients than healthy controls. A screen of several common urinary tract infections (UTI)-related organisms showed strong induction of TLR2-signalling in the same assay. Taken together, these results indicate that two different markers of TLR2-activity - urinary TLR2-stimulants, and serum sTLR2 levels - are significantly elevated in MS patients compared to healthy controls.

Item Type: Journal Article
Keywords: Toll-like receptor 2, soluble TLR2, multiple sclerosis, urinary tract infection, biomarker, inflammation
Faculty: Faculty of Science & Technology
Depositing User: Dr Clett Erridge
Date Deposited: 12 Mar 2018 14:22
Last Modified: 19 Mar 2018 15:58
URI: http://arro.anglia.ac.uk/id/eprint/702821

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