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

• Published in: Journal of autoimmunity Vol. 88; pp. 83 - 90
• Main Authors: Kalluri, Sudhakar Reddy, Grummel, Verena, Hracsko, Zsuzsanna, Pongratz, Viola, Pernpeintner, Verena, Gasperi, Christiane, Buck, Dorothea, Hemmer, Bernhard
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2018
• Subjects: Anti-drug antibodies; Antigenic epitope; Interferon beta; Multiple sclerosis; Neutralizing antibodies; T cell; Multiple sclerosis; Anti-drug antibodies; Neutralizing antibodies; Antigenic epitope; T cell; Interferon beta
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2017.10.003

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. •Identification and characterization of T cell responses in IFN-β treated patients.•T cell responses against IFN-β correlate with anti-drug antibodies and loss of biological activity.•Anti-drug antibody associated T cells have Th2 phenotype and target the IFN-β125-159 epitope.