scholarly journals Peripheral Biomarkers in Multiple Sclerosis Patients Treated with Interferon-Beta

2021 ◽  
Author(s):  
Andreia Monteiro ◽  
Ana Mafalda Fonseca ◽  
Artur Paiva

Multiple sclerosis is a relapsing and eventually progressive disorder of the central nervous system that continues to challenge researchers who try to understand the pathogenesis of the disease and prevent its progression. Interferon-beta is the most widely prescribed treatment for MS. Peripheral blood seems to mirror the immunological disturbances that underlie MS, which could represent the migration patterns between periphery and other tissues according to the clinical phase of the disease. Based on this assumption, several studies point to significant alterations in peripheral blood homeostasis of different subpopulations of T cells, like γδ T cells or Th1, Th2 and Th17 functional subsets; of B cells subpopulations; and of innate cells like monocytes and dendritic cells. The main goal of this chapter is to make an in-depth review of the major findings described in the literature that correlate specific alterations on different leukocytes subpopulations with disease status, and which therefore have the potential to constitute a peripheral biomarker of disease progression.

1994 ◽  
Vol 52 (2) ◽  
pp. 139-146 ◽  
Author(s):  
Martin H.G. Rep ◽  
Rogier Q. Hintzen ◽  
Chris H. Polman ◽  
RenéA.W. van Lier

2010 ◽  
Vol 71 (5) ◽  
pp. 437-441 ◽  
Author(s):  
Giovanni Frisullo ◽  
Viviana Nociti ◽  
Raffaele Iorio ◽  
Domenico Plantone ◽  
A. Katia Patanella ◽  
...  

2011 ◽  
Vol 18 (6) ◽  
pp. 788-798 ◽  
Author(s):  
M Chiarini ◽  
F Serana ◽  
C Zanotti ◽  
R Capra ◽  
S Rasia ◽  
...  

Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy. Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population. Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the ‘central memory-like’ Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy. Conclusions: The selective increase of ‘central memory-like’ subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.


2001 ◽  
Vol 7 (3) ◽  
pp. 145-150 ◽  
Author(s):  
J Killestein ◽  
B F Den Drijver ◽  
W L Van der Graaff ◽  
B MJ Uitdehaag ◽  
C H Polman ◽  
...  

Objective: To evaluate the expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients with either relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP) MS and healthy controls (HC). Background: MS is an immune-mediated disease and cytokines have been hypothesized to contribute significantly to disease progression. Compared to the relapse-onset (RR, SP) form of the disease, PPMS patients have different clinical, immunological and pathological features. Surprisingly, the ability of their circulating T cells to produce immunoregulatory cytokines has not been extensively studied so far. Methods: Seventy-two MS patients (24 RR, 26 SP, 22 PP) and 34 HC were studied. Stimulated peripheral blood derived CD4+ and CD8+ T cells were analyzed for IFN-g, IL-2, TNF-a, IL-4, IL-10 and IL-13 production. Results: MS patients express significantly more CD4+ and CD8+ T cells producing IFN-g compared to HC. Compared to the other forms of the disease, PPMS patients display a significant decrease in CD4+ T cells producing IL-2, IL-13 and TNF-a and a significant increase in CD8+ T cells producing IL-4 and IL-10. Conclusions: The data presented here demonstrate that patients with PPMS express less pro- and more anti-inflammatory cytokine producing T cells compared to the relapse-onset form of the disease, confirming the view on PPMS as a distinct disease entity.


2018 ◽  
Vol 88 ◽  
pp. 83-90 ◽  
Author(s):  
Sudhakar Reddy Kalluri ◽  
Verena Grummel ◽  
Zsuzsanna Hracsko ◽  
Viola Pongratz ◽  
Verena Pernpeintner ◽  
...  

2005 ◽  
Vol 30 (4) ◽  
pp. 453-456 ◽  
Author(s):  
S. Vivekanandhan ◽  
C. C. Soundararajan ◽  
M. Tripathi ◽  
M. C. Maheshwari

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