Biomarkers in multiple sclerosis

Housley, William; Pitt, David; Hafler, David A.

doi:10.1016/j.clim.2015.06.015

Cited by 144 publications

(111 citation statements)

References 141 publications

(25 reference statements)

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“…The concentration of NFL is shown to be increased in CSF at all stages of MS, it is elevated with the presence of active MRI lesions, and the highest concentrations are found during acute relapses (43). Importantly, long-term follow-up studies have demonstrated that the NFL concentrations found at initial diagnosis of MS were predictive of disease severity and advancement to secondary progressive disease (44). Thus, our findings suggest that the Th1-skewed activation of Vδ1 cells is related to axonal damage.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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 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-γ-producing Vδ1 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 Vδ1 T lymphocytes as an early marker of MS and a possible link to understanding the disease etiology.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…Investigation of the immunological consequences of these risk factors should increase understanding of MS pathogenesis and enable the development of better therapies. This genetic knowledge should also be translated to develop clinically useful biomarkers [4] aimed at the key questions of when to start treatment (and in whom), which drug to select (from several now available) and when to change. Despite knowledge that early effective treatment for autoimmune disease can be critical in delaying progression [5] and individuals respond to some therapies better than others, practical biomarkers have not yet been identified to guide clinical management of MS.…”

Section: Introductionmentioning

confidence: 99%

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

McKay

Gatt

Fewings

et al. 2016

Clinical Immunology

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Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p < 0.028 for TBX21) and demonstrate longitudinal stability (p<10 -4 ) and high heritability (h 2 =0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were underrepresented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate.

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“…Expectedly, the number of neuron in bFGF-GMSs group was more than that in the free bFGF solution group ( P <0.05, Fig 5C). GFAP is a marker of astrocyte activation in the nervous system [20, 21]. Astrocytes usually promoted the formation of scar in chronic spinal cord injury, which hindered regeneration of axon.…”

Section: Resultsmentioning

confidence: 99%

Implantable porous gelatin microspheres sustained release of bFGF and improved its neuroprotective effect on rats after spinal cord injury

Tian

ZhuGe

et al. 2017

PLoS ONE

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In this study, porous gelatin microspheres (GMSs) were constructed to improve the neuroprotective effect of basic fibroblast growth factor (bFGF) on spinal cord injury. GMSs were prepared by a W/O emulsion template, followed by cross-linking, washing and drying. The particle sizes and surface porosity of the blank GMSs were carefully characterized by scan electronic microscopy. The blank GMSs have a mean particle size of 35μm and theirs surface was coarse and porous. bFGF was easily encapsulated inside the bulk GMSs through diffusion along the porous channel. 200μg of bFGF was completely encapsulated in 100mg of GMSs. The bFGF-loaded GMSs displayed a continuous drug release pattern without an obvious burst release over two weeks in vitro. Moreover, the therapeutic effects of bFGF-loaded GMSs were also evaluated in spinal cord injury rat model. After implantation of bFGF-loaded GMSs, the recovery of the motor function of SCI rats were evaluated by behavioral score and foot print experiment. The motor function of SCI rats treated with bFGF-loaded GMSs was more obvious than that treated with free bFGF solution (P<0.05). At the 28th days after treatment, rats were sacrificed and the injured spinal were removed for histopathological and apoptosis examination. Compared with treatment with free bFGF solution, treatment with bFGF-loaded GMSs resulted in a less necrosis, less infiltration of leukocytes, and a reduced the cavity ratio and less apoptotic cells in injured spinal(P<0.01), indicating its better therapeutic effect. Implantable porous GMSs may be a potential carrier to deliver bFGF for therapy of spinal cord injury.

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Biomarkers in multiple sclerosis

Cited by 144 publications

References 141 publications

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

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

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

Implantable porous gelatin microspheres sustained release of bFGF and improved its neuroprotective effect on rats after spinal cord injury

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