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The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker

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posted on 2019-08-01, 13:46 authored by MJ Hossain, E Morandi, R Tanasescu, N Frakich, M Caldano, D Onion, TA Faraj, C Erridge, B Gran
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 signaling 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 HC 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 cells transfectant reporter assay, were significantly higher in urine of MS patients than HC. A screen of several common urinary tract infections (UTI)-related organisms showed strong induction of TLR2-signaling 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 HC.

Funding

The study was supported by a McDonald fellowship to MH from the Multiple Sclerosis International Federation (MSIF) and the National Multiple Sclerosis Society (NMSS) of USA. Research in Dr. Gran’s lab was supported by a grant from the Italian Multiple Sclerosis Society and its Foundation, entitled “Role of TLR2 in the activation of inflammation by infections in Multiple Sclerosis” (FISM cod. 2013/R/14). Dr. Bertolotto was supported by a grant from the Italian Multiple Sclerosis Society and its Foundation (FISM cod. 2014/PMS/1).

History

Citation

Frontiers in Immunology, 2018, 9

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Frontiers in Immunology

Publisher

Frontiers

eissn

1664-3224

Acceptance date

2018-02-20

Copyright date

2018

Available date

2019-08-01

Language

en

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