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J Autoimmun. 2018 Mar;88:83-90. doi: 10.1016/j.jaut.2017.10.003. Epub 2017 Oct 21.

Interferon-beta specific T cells are associated with the development of neutralizing antibodies in interferon-beta treated multiple sclerosis patients.

Author information

1
Klinikum rechts der Isar, Department of Neurology, School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
2
Klinikum rechts der Isar, Department of Neurology, School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. Electronic address: hemmer@tum.de.

Abstract

Beta-interferons are still among the most commonly used drugs to treat Multiple Sclerosis (MS). The use of beta-interferons is limited by the development of anti-drug antibodies (ADA), which may abrogate the treatment effect of the drug. Although the antibody response has been well studied, little is known about the T cell response to interferon-beta (IFN-β). We investigated T cell responses in four treatment naïve MS patients and twenty-three patients treated with IFN-β who had or had not developed ADA to IFN-β. T cell responses were determined by split-well and primary proliferation assays against different IFN-β protein preparations and a set of overlapping peptides covering the full sequence of IFN-β. T cell responses to IFN-β were observed in all donors. ADA positive patients showed higher T cell responses to IFN-β protein than ADA negative patients and untreated controls. We identified two immunodominant regions; T cell responses to IFN-β1-40 were observed in all patients independent of ADA status, while T cell responses to IFN-β125-159 were stronger in ADA positive than ADA negative patients. IFN-β specific T cell responses were HLA class II restricted and in ADA positive patients skewed towards a Th2 phenotype. In IFN-β treated patients we observed a correlation between IFN-β specific T cell responses, serum ADA titer and loss of biological activity of IFN-β treatment. Our studies demonstrate the occurrence of an antigen specific HLA class II restricted Th2 T cell response associated with the development of ADA in IFN-β treated patients.

KEYWORDS:

Anti-drug antibodies; Antigenic epitope; Interferon beta; Multiple sclerosis; Neutralizing antibodies; T cell

PMID:
29066027
DOI:
10.1016/j.jaut.2017.10.003
[Indexed for MEDLINE]

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