The development of clinical activity in relapsing–remitting MS is associated with a decrease of FasL mRNA and an increase of Fas mRNA in peripheral blood

Lopatinskaya, Luba; Boxel-Dezaire, Anette H.H. van; Barkhof, Frederik; Polman, Chris H.; Lucas, C.J.; Nagelkerken, Lex

doi:10.1016/s0165-5728(03)00089-4

Cited by 17 publications

(8 citation statements)

References 41 publications

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“…T-cell apoptosis is regulated in part by the Fas-FasL system. Evidence has shown that the level of FasL expression is decreased during MS relapse, a finding consistent with the increased resistance of the T cells to apoptosis [38]. When we investigated the relationship between RGC-32 and FasL in RRMS patients, we found that the levels of RGC-32 and FasL mRNAs in peripheral blood mononuclear cells (PBMCs) were significantly decreased during relapses when compared to those of stable patients, and they were significantly increased in stable patients when compared to controls [39].…”

Section: Introductionmentioning

confidence: 66%

The complement system as a biomarker of disease activity and response to treatment in multiple sclerosis

et al. 2017

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Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The complement system has an established role in the pathogenesis of MS, and evidence suggests that its components can be used as biomarkers of disease-state activity and response to treatment in MS. Plasma C4a levels have been found to be significantly elevated in patients with active relapsing-remitting MS (RRMS), as compared to both controls and patients with stable RRMS. C3 levels are also significantly elevated in the cerebrospinal fluid (CSF) of patients with RRMS, and C3 levels are correlated with clinical disability. Furthermore, increased levels of factor H can predict the transition from relapsing to progressive disease, since factor H levels have been found to increase progressively with disease progression over a 2-year period in patients transitioning from RRMS to secondary progressive (SP) MS. In addition, elevations in C3 are seen in primary progressive (PP) MS. Complement components can also differentiate RRMS from neuromyelitis optica. Response gene to complement (RGC)-32, a novel molecule induced by complement activation, is a possible biomarker of relapse and response to glatiramer acetate (GA) therapy, since RGC-32 mRNA expression is significantly decreased during relapse and increased in responders to GA treatment. The predictive accuracy of RGC-32 as a potential biomarker (by ROC analysis) is 90% for detecting relapses and 85% for detecting a response to GA treatment. Thus, complement components can serve as biomarkers of disease activity to differentiate MS subtypes and to measure response to therapy.

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Section: Introductionmentioning

confidence: 66%

The complement system as a biomarker of disease activity and response to treatment in multiple sclerosis

et al. 2017

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“…Higher levels of the cell surface ligands Fas and FasL which promote apoptosis of activated T cells predict slower long-term disability progression in MS [41]. During acute relapse, serum FasL declines while Fas increases [42]. Survivin, a molecule that inhibits apoptosis of activated T cells, was found to be increased during active disease and down-regulated by IFN-β [43,44].…”

Section: T Cell Subsetsmentioning

confidence: 99%

Biomarkers of disease activity in multiple sclerosis

Graber

Dhib‐Jalbut²

2011

Journal of the Neurological Sciences

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“…Low levels of Fas mRNA were associated with higher disability. Previously it has been reported that FasR mRNA is up-regulated in MS patients [36], [37]. It has also been shown that T cells from MS patients with are more resistant to apoptosis mediated by the FasR than cells from healthy individuals [9], [38], [39].…”

Section: Discussionmentioning

confidence: 98%

MK2 and Fas Receptor Contribute to the Severity of CNS Demyelination

et al. 2014

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Models of inflammatory or degenerative diseases demonstrated that the protein-kinase MK2 is a key player in inflammation. In this study we examined the role of MK2 in MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. In MK2-deficient (MK2−/−) mice we found a delayed onset of the disease and MK2−/− mice did not recover until day 24 after EAE induction. At this day a higher number of leukocytes in the CNS of MK2−/− mice was found. TNFα was not detectable in serum of MK2−/− mice in any stage of EAE, while high TNFα levels were found at day 16 in wild-type mice. Further investigation revealed an increased expression of FasR mRNA in leukocytes isolated from CNS of wild-type mice but not in MK2−/− mice, however in vitro stimulation of MK2−/− splenocytes with rmTNFα induced the expression of FasR. In addition, immunocomplexes between the apoptosis inhibitor cFlip and the FasR adapter molecule FADD were only detected in splenocytes of MK2−/− mice at day 24 after EAE induction. Moreover, the investigation of blood samples from relapsing-remitting multiple sclerosis patients revealed reduced FasR mRNA expression compared to healthy controls. Taken together, our data suggest that MK2 is a key regulatory inflammatory cytokines in EAE and multiple sclerosis. MK2−/− mice showed a lack of TNFα and thus might not undergo TNFα-induced up-regulation of FasR. This may prevent autoreactive leukocytes from apoptosis and may led to prolonged disease activity. The findings indicate a key role of MK2 and FasR in the regulation and limitation of the immune response in the CNS.

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The development of clinical activity in relapsing–remitting MS is associated with a decrease of FasL mRNA and an increase of Fas mRNA in peripheral blood

Cited by 17 publications

References 41 publications

The complement system as a biomarker of disease activity and response to treatment in multiple sclerosis

The complement system as a biomarker of disease activity and response to treatment in multiple sclerosis

Biomarkers of disease activity in multiple sclerosis

MK2 and Fas Receptor Contribute to the Severity of CNS Demyelination

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