Correlation between anti-interferon-β binding and neutralizing antibodies in interferon-β-treated multiple sclerosis patients

TY - JOUR

T1 - Correlation between anti-interferon-β binding and neutralizing antibodies in interferon-β-treated multiple sclerosis patients

AU - Jensen, P E H

AU - Sellebjerg, F

AU - Søndergaard, H B

AU - Sørensen, P S

N1 - © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

PY - 2012/10

Y1 - 2012/10

N2 - Background and purpose: Measurements of binding antibodies (BAbs), neutralizing antibodies (NAbs) and MX1 mRNA expression are used to analyse the immunological reactions in patients with MS treated with IFN-β. The correlations between these are yet not fully understood. Methods: We measured BAbs and NAbs to IFN-β in 110 serum samples from 83 patients with MS treated with IFN-β, and in a subgroup, antibody titre was compared with corresponding expressions of MX1 mRNA. The methods used were capture ELISA assay, luciferase reporter gene assay and mRNA RT-PCR for MX1 gene expression. Results: There were significant correlations between binding, neutralizing and MX1 results. Cut-off values are suggested for the definition of samples of BAbs and NAbs as negative, positive and grey zones. Naturally occurring groups of low and high antibody titres were identified by the correlation between BAbs and NAbs, probably as a result of an immunological maturation process of antibodies. The low-titre group had lower correlations between BAbs and NAbs than the high-titre group. Conclusions: High correlation is demonstrated between the results obtained by the three methods, and we suggest the possibility of using ELISA measurements of BAbs to identify patients with high titres of anti-IFN-β antibodies that block the biological response to IFN-β. Ιn patients with low titres, we suggest to supplement ELISA with measurement of MX1 mRNA to establish whether the bioavailability of IFN-β is preserved.

AB - Background and purpose: Measurements of binding antibodies (BAbs), neutralizing antibodies (NAbs) and MX1 mRNA expression are used to analyse the immunological reactions in patients with MS treated with IFN-β. The correlations between these are yet not fully understood. Methods: We measured BAbs and NAbs to IFN-β in 110 serum samples from 83 patients with MS treated with IFN-β, and in a subgroup, antibody titre was compared with corresponding expressions of MX1 mRNA. The methods used were capture ELISA assay, luciferase reporter gene assay and mRNA RT-PCR for MX1 gene expression. Results: There were significant correlations between binding, neutralizing and MX1 results. Cut-off values are suggested for the definition of samples of BAbs and NAbs as negative, positive and grey zones. Naturally occurring groups of low and high antibody titres were identified by the correlation between BAbs and NAbs, probably as a result of an immunological maturation process of antibodies. The low-titre group had lower correlations between BAbs and NAbs than the high-titre group. Conclusions: High correlation is demonstrated between the results obtained by the three methods, and we suggest the possibility of using ELISA measurements of BAbs to identify patients with high titres of anti-IFN-β antibodies that block the biological response to IFN-β. Ιn patients with low titres, we suggest to supplement ELISA with measurement of MX1 mRNA to establish whether the bioavailability of IFN-β is preserved.

U2 - 10.1111/j.1468-1331.2012.03721.x

DO - 10.1111/j.1468-1331.2012.03721.x

M3 - Journal article

C2 - 22564111

SN - 1351-5101

VL - 19

SP - 1311

EP - 1317

JO - European Journal of Neurology

JF - European Journal of Neurology

IS - 10

ER -