Immunomodulatory potential of anti-IFN-beta antibodies on monocyte-derived macrophages.

Abstract

Multiple sclerosis (MS) is a disabling neurological disease with an unknown etiology, where the recombinant interferon beta (rIFNβ) is the most established treatment. However, the development of anti-IFNβ antibodies has posed a significant therapeutic drawback. In this study, the interaction between anti-IFNβ antibodies and macrophages was investigated to assess the effects on the immune system. Using magnetic beads, anti-IFNβ antibodies were extracted from MS patients' sera positive for anti-IFNβ antibodies. A negative control (antibody-negative situation) and a baseline control were obtained in parallel. Bead or extracted beadantibody complexes were then incubated with monocyte-derived human macrophages. After incubation, macrophage cultures were tested for 91 immunologically relevant gene expressions by RT-PCR. A Gene expression difference between antibody positive and negative situations was hypothesized to reflect the direct effects between antibodies and macrophages. Thus, 37-39 genes were either up-regulated or downregulated due to this direct interaction. Of these, only 2-4 genes were up-regulated, and the rest were down-regulated. These observations suggest that anti-IFNβ antibodies have an overall suppressive effect on immunologically relevant gene activity when antibodies interact with macrophages. The fate and effects of circulating anti-IFNβ antibodies are mainly unknown. With the observations obtained at level, such effects, especially from an immunological point of view, are suppressive on immunocompetent cells such as macrophages. However, verification is necessary.