Limits...
Endogenous and recombinant type I interferons and disease activity in multiple sclerosis.

Sellebjerg F, Krakauer M, Limborg S, Hesse D, Lund H, Langkilde A, Søndergaard HB, Sørensen PS - PLoS ONE (2012)

Bottom Line: Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells), and this effect was associated with less MRI disease activity.In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity.However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy.

View Article: PubMed Central - PubMed

Affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. sellebjerg@dadlnet.dk

ABSTRACT
Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells), and this effect was associated with less MRI disease activity. IFN-β therapy reduced CD49d expression on CD4+CD26(high) T cells, and the percentage of CD4+CD26(high) T cells that were CD49d(high) correlated with clinical and MRI disease activity in patients treated with IFN-β. Treatment with IFN-β also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy.

Show MeSH

Related in: MedlinePlus

T cell activation and relapse risk.Relationship between CD4+ T cell expression of HLA-DR and relapse risk in 39 patients from whom blood samples were obtained 36–48 hours after an injection of interferon-β. Patients were dichotomized around the median and relapse risk was analysed in Kaplan-Meier plots and with the log-rank test in all patients and in subgroups of patients with a shorter duration of treatment or disease duration.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3368920&req=5

pone-0035927-g002: T cell activation and relapse risk.Relationship between CD4+ T cell expression of HLA-DR and relapse risk in 39 patients from whom blood samples were obtained 36–48 hours after an injection of interferon-β. Patients were dichotomized around the median and relapse risk was analysed in Kaplan-Meier plots and with the log-rank test in all patients and in subgroups of patients with a shorter duration of treatment or disease duration.

Mentions: The relationship between CD40 expression on dendritic cells and HLA-DR expression on CD4+ T cells and relapse risk was further analysed in the 40 patients from whom blood samples were obtained 36–48 hours after an injection of IFN-β. In this cohort there was no relationship between CD40 expression on dendritic cells and relapse risk. However, patients with a percentage of HLA-DR positive CD4+ T cells above median had a higher relapse risk than patients with below median values (Figure 2). This relationship was highly significant in patients with a disease duration of less than 5 years (n = 19, p = 0.003) and in patients treated with IFN-β for less than two years (n = 21, p = 0.004) (Figure 2). Gd-enhancing MRI lesions were observed in 10/40 of these patients but were not an independent predictor of relapse risk in the multivariate analysis.


Endogenous and recombinant type I interferons and disease activity in multiple sclerosis.

Sellebjerg F, Krakauer M, Limborg S, Hesse D, Lund H, Langkilde A, Søndergaard HB, Sørensen PS - PLoS ONE (2012)

T cell activation and relapse risk.Relationship between CD4+ T cell expression of HLA-DR and relapse risk in 39 patients from whom blood samples were obtained 36–48 hours after an injection of interferon-β. Patients were dichotomized around the median and relapse risk was analysed in Kaplan-Meier plots and with the log-rank test in all patients and in subgroups of patients with a shorter duration of treatment or disease duration.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368920&req=5

pone-0035927-g002: T cell activation and relapse risk.Relationship between CD4+ T cell expression of HLA-DR and relapse risk in 39 patients from whom blood samples were obtained 36–48 hours after an injection of interferon-β. Patients were dichotomized around the median and relapse risk was analysed in Kaplan-Meier plots and with the log-rank test in all patients and in subgroups of patients with a shorter duration of treatment or disease duration.
Mentions: The relationship between CD40 expression on dendritic cells and HLA-DR expression on CD4+ T cells and relapse risk was further analysed in the 40 patients from whom blood samples were obtained 36–48 hours after an injection of IFN-β. In this cohort there was no relationship between CD40 expression on dendritic cells and relapse risk. However, patients with a percentage of HLA-DR positive CD4+ T cells above median had a higher relapse risk than patients with below median values (Figure 2). This relationship was highly significant in patients with a disease duration of less than 5 years (n = 19, p = 0.003) and in patients treated with IFN-β for less than two years (n = 21, p = 0.004) (Figure 2). Gd-enhancing MRI lesions were observed in 10/40 of these patients but were not an independent predictor of relapse risk in the multivariate analysis.

Bottom Line: Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells), and this effect was associated with less MRI disease activity.In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity.However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy.

View Article: PubMed Central - PubMed

Affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. sellebjerg@dadlnet.dk

ABSTRACT
Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells), and this effect was associated with less MRI disease activity. IFN-β therapy reduced CD49d expression on CD4+CD26(high) T cells, and the percentage of CD4+CD26(high) T cells that were CD49d(high) correlated with clinical and MRI disease activity in patients treated with IFN-β. Treatment with IFN-β also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy.

Show MeSH
Related in: MedlinePlus