Dataset Information

High Interferon-? Uniquely in V?1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis.

ABSTRACT: We have identified a population of T lymphocytes in peripheral blood, V?1 TCR?? T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-? in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-? production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These V?1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and which include reactivity to the myelin glycosphingolipid sulfatide. Importantly, patients treated with natalizumab, blocking leukocyte transmigration to central nervous system, had completely normalized levels of interferon-?-producing V?1 T lymphocytes. A biomarker and early sign of demyelinating disease in MS is much warranted and would help identify immunopathogenesis and prognosis of disease as well as monitor success with adequate treatment. The present study identifies the V?1 T lymphocytes as an early marker of MS and a possible link to understanding the disease etiology.

SUBMITTER: Singh AK

PROVIDER: S-EPMC5343019 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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High Interferon-γ Uniquely in Vδ1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis.

Singh Avadhesh Kumar AK Novakova Lenka L Axelsson Markus M Malmeström Clas C Zetterberg Henrik H Lycke Jan J Cardell Susanna L SL

Frontiers in immunology 20170309

We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-γ production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These Vδ1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and whi ...[more]

PMID: 28337205

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Project description:BackgroundExpression of soluble CD163 (sCD163), a macrophage/microglia biomarker, is increased in inflammatory conditions, and sCD163 levels in the cerebrospinal fluid (CSF) have recently been shown to be elevated in patients with multiple sclerosis (MS): the sCD163 CSF/serum ratio was elevated in patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and clinically isolated syndrome (CIS) compared with symptomatic controls.ObjectiveTo investigate the contributions of the sCD163 CSF/serum ratio to a biomarker panel focusing on inflammation and axonal degeneration in newly diagnosed MS; thus optimising a diagnostic biomarker panel for MS.MethodsAfter a full MS diagnostic work-up, including collection of paired samples of CSF and serum, 125 patients were included in this study. Patients were divided into groups based on their diagnosis, and patients with normal clinical and paraclinical findings were defined as symptomatic controls. Serum and CSF levels, ratios, and indices of sCD163, CXCL13, osteopontin, neopterin, and CSF levels of neurofilament light polypeptide were determined by enzyme-linked immunosorbent assays (ELISAs). For sCD163 the results constitute a post-hoc analysis of already published data.ResultsAll tested biomarkers, notably the sCD163 ratio, the CXCL13 ratio, the NEO ratio, the CSF level of NfL, the IgG index, and the serum level of OPN, were significantly correlated to RRMS, PPMS, and/or CIS. The individual biomarkers in single tests had a lower performance than the IgG index, however, their combined receiver operating characteristic (ROC) curve demonstrated excellent diagnostic discriminatory power.ConclusionThe biomarker panel showed distinct profiles for each patient group and could be a valuable tool for clinical differentiation of MS subgroups. The combined ROC analysis showed that sCD163 contributes positively as a diagnostic marker to a panel of established MS biomarkers. Patients with PPMS were demonstrated to have significantly elevated levels of both inflammatory and degenerative markers.

Dataset Information

High Interferon-? Uniquely in V?1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis.

Publications

High Interferon-γ Uniquely in Vδ1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis.

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