Interferon beta (IFNβ) is used as a first-line treatment for multiple sclerosis (MS) and is injected intramuscularly or subcutaneously (s.c.). The subcutaneous route is considered more immunogenic as it is associated with increased antidrug antibody-positive patients. The skin contains dendritic cells (DCs) and it is unclear whether these contribute to immunogenicity. To assess the effect of IFNβ on skin-resident cells, IFNβ was injected intradermally (i.d.) ex vivo using a human skin explant model or s.c. in vivo in MS patients. Ex vivo, intradermal IFNβ injections reduced migration and enhanced surface CD86 expression of dermal DCs, and an increased expression of HLA-DR+ was observed in skin biopsies taken after subcutaneous IFNβ injection (in vivo). In both models, IFNβ elevated the expression of several inflammatory cytokines when compared to the control biopsies. Our results show that 3 different IFNβ preparations, normalized in dose and injection site, induce similar immune responses, suggesting that the differences in immunogenicity are likely due to the route and frequency of administration.
Keywords: anti-drug antibodies; immunogenicity; immunomodulations by IFNs.